Spectral distribution of SPARC photoinjector electrons

SPARC is a photo-injector for production of high-brightness lowemittance electron beams to drive a FEL experiment in various configurations, including SASE-FEL radiation of 1–10nm (SPARCX project). Due to a high-brightness source, the SPARC facility can be used to study the physics of ultrashort beams, plasma-wave based acceleration, production of X-rays by means of Compton backscattering, channeling of electron beams and other experiments. The initial process of electron beam generation inside the RF gun determines the main parameters of the electron beam. Interaction of electrons with high-frequency laser beam leads to modulation of the electron beam. In this paper we present electron beam spectral distribution for SPARC photoinjector parameters. The estimate of electron beam energy loss for such electron distribution also is given

Клиническая значимость фенотипа иммунных клеток опухолевой стромы рака предстательной железы

Introduction. Prostate cancer is by far the most frequently diagnosed cancer among the male population and ranks fifth in the world in terms of mortality rates among malignant neoplasms. Today it is known that the tumor microenvironment plays an important role in the pathogenesis of the disease. Abundant data has accumulated indicating that cells of the inflammatory infiltrate of the tumor are involved in the onset, progression and response to treatment in cases of prostate cancer. However, their role in the context of disease progression has not yet been determined. In this work, we studied the phenotype of inflammatory infiltrate of prostate cancer and its association with the clinical and morphological characteristics of patients.The study objective is to determine the features of the inflammatory infiltrate of prostate cancer and its association with the clinical and morphological characteristics of patients with this disease.Materials and methods. The study included tumor samples obtained from 31 patients with prostate cancer. The expression of CD3, CD8, FoxP3, CD68, PU.1, CD204, CD163, IDO1, PD-L1 (programmed death-ligand 1) was assessed by immunohistochemistry. The relationship between markers and clinical and morphological characteristics was assessed using the nonparametric Mann–Whitney test and Fisher’s exact test. Spearman’s rank correlation coefficient was used to analyze the correlations between contents of cells of different phenotypes. Differences were considered statistically significant at p <0.05.Results. This study describes the features of the stroma of prostate cancer. We have shown that an increased content of CD204+ cells is associated with an older age of patients (p = 0.0026), and the number of CD163+ and CD8+ cells with no metastases to regional lymph nodes (p = 0.0067 and p = 0.0069, respectively). It has been shown that PU.1 can be used as a general marker of macrophages. We also found significant correlations between the level of PU.1 and PD-L1 in the stroma (r = 0.421; p = 0.018) and IDO1 in the stroma (r = 0.557; p = 0.001) and in tumor cells (r = 0.393; p = 0.029), CD68 with IDO1 in the stroma (r = 0.535; p = 0.002), CD163 with PD-L1 and IDO1 in the stroma (r = 0.399; p = 0.026 and r = 0.220; p = 0.026, respectively).Conclusion. In this work, the characteristics of the stroma of prostate cancer were investigated. Our data indicate that tumor associated macrophages are the main cells expressing PD-L1 and IDO1 in the tumor stroma in the case of prostate cancer. Increased expression of IDO1 in tumor tissue is associated with the immunosuppressive phenotype of the inflammatory infiltrate. The fact that the number of macrophages directly correlates with the number of T-lymphocytes in the prostate stroma, and the number of M2 macrophages with cytotoxic T-cells indicates the interaction of the mechanisms of innate and acquired immunity during the progression of prostate cancer.Введение. Рак предстательной железы на сегодняшний день является наиболее часто диагностируемым онкологическим заболеванием среди мужского населения и занимает 5-е место в мире по показателям смертности среди злокачественных новообразований. Известно, что микроокружение опухоли играет большую роль в патогенезе заболевания. Накоплено много данных, свидетельствующих о том, что клетки воспалительного инфильтрата опухоли участвуют в возникновении, прогрессии и ответе на лечение в случаях рака предстательной железы. Однако их роль в контексте прогрессии заболевания еще не определена. в статье представлено исследование фенотипа воспалительного инфильтрата рака предстательной железы и его ассоциации с клинико-морфологическими характеристиками пациентов.Цель исследования – определение особенностей воспалительного инфильтрата рака предстательной железы и его ассоциации с клинико-морфологическими характеристиками пациентов с данным заболеванием.Материалы и методы. В исследование были включены образцы опухолей, полученные от 31 пациента с раком предстательной железы. С помощью иммуногистохимического исследования проанализирована экспрессия CD3, CD8, FoxP3, CD68, PU.1, CD204, CD163, IDO1 и PD-L1 (лиганда рецептора программируемой клеточной гибели 1). Для определения взаимосвязи маркеров и клинико-морфологических характеристик пациентов использовались непараметрический критерий манна–Уитни и точный критерий фишера. Для анализа корреляций между содержанием клеток различных фенотипов применяли коэффициент ранговой корреляции спирмена. во всех анализах значение p ≤0,05 считалось статистически значимым.Результаты. В ходе исследования определены особенности стромы рака предстательной железы. Было продемонстрировано, что повышенное содержание CD204+-клеток ассоциировано с более старшим возрастом пациентов (р = 0,0026), а количество CD163+- и CD8+-клеток – с отсутствием метастазов в регионарные лимфатические узлы (р = 0,0067 и р = 0,0069 соответственно). Показано, что PU.1 может быть использован как общий маркер макрофагов. Также мы выявили достоверные корреляции уровня PU.1 с PD-L1 в строме (r = 0,421; р = 0,018), IDO1 в строме (r = 0,557; p = 0,001) и опухолевых клетках (r = 0,393; р = 0,029), а также CD68 c IDO1 (r = 0,535; p = 0,002) и сD163 c PDL1 и IDO1 в строме (r = 0,399; p = 0,026 и r = 0,220; p = 0,026 соответственно).Заключение. Были исследованы характеристики стромы рака предстательной железы. полученные данные указывают на то, что основными клетками, экспрессирующими PD-L1 и IDO1 в строме опухоли, в случае рака предстательной железы являются макрофаги, инфильтрирующие опухоль. Повышенная экспрессия IDO1 в опухолевой ткани ассоциирована с иммуносупрессорным фенотипом воспалительного инфильтрата. тот факт, что количество макрофагов прямо коррелирует с количеством т-лимфоцитов в строме рака предстательной железы, а уровень содержания макрофагов 2-го типа – с цитотоксическими т-клетками, свидетельствует о взаимодействии механизмов врожденного и приобретенного иммунитета в процессе прогрессии опухоли

Иммуносупрессорные особенности фенотипа стромы опухолей почки различных гистологических типов

Background. Renal cell carcinoma is a heterogeneous group of tumors characterized by high vascularization and immunogenicity. Immunotherapy has made a breakthrough in the treatment of this pathology, however, the lack of development of criteria for its use does not allow to achieve even greater success. It is known that the tumor stroma plays an important role in the success of immunotherapy. Among the various histological types of kidney tumors, the stroma of the clear cell renal cell carcinoma has been studied in sufficient detail. However, the remaining histological types are practically not studied.Objective: description of the immunosuppressive phenotype of the stroma of kidney tumors of various histological types.Materials and methods. The study included tumor samples obtainedfrom 44patients with renal cell carcinoma of various histological types (16 samples of chromophobe cancer, 15 samples of clear cell and 13 samples of papillary renal cell carcinoma). The method of immunohis-tochemistry evaluated the expression of tumor stromal markers, namely CD68, CD206, PU.1, CD3, IDO1 and PD-L1 in the studied samples.Results. Analysis of the total number of macrophages associated with the tumor showed that the smallest number is observed in samples of chromophobe renal cancer, while in the samples of clear cell cancer their number is greatest. A similar situation is observed for T-cells: the largest number of CD3+ cells is observed in clear cell tumors. In chromophobe and papillary tumors, their number is reduced. Papillary tumors are also characterized by an almost complete absence of expression of PD-L1 and IDO1 compared to other histological types of kidney tumors. We also showed that for PU.1 there is a strong positive correlation between its quantity and localization, as in CD68. Thus, PU.1 can be used as a general marker for describing stromal macrophages in kidney tumors.Conclusion. The study showed that kidney tumors of various histological types strongly and significantly differ in the composition of their microenvironment. These data, of course, must be considered when choosing immune therapy in the treatment of this pathology.Введение. Почечно-клеточная карцинома представляет собой гетерогенную группу опухолевых заболеваний, характеризующуюся высокой васкуляризированностью и иммуногенностью. Иммунотерапия совершила прорыв в лечении данной патологии, однако недостаточность выработки критериев ее применения не позволяет добиться еще больших успехов. Известно, что в успехе иммунотерапии немаловажную роль играет опухолевая строма. Среди различных гистологических типов опухолей почки строма светлоклеточного варианта почечно-клеточной карциномы изучена достаточно подробно. Однако остальные гистологические типы практически не изучены.Цель исследования — описание иммуносупрессорного фенотипа стромы опухолей почки различных гистологических типов. Материалы и методы. В исследование были включены образцы опухолей, полученные от 44 больных почечно-клеточным раком различных гистологических типов (16 образцов хромофобного, 15 образцов светлоклеточного и 13 образцов папиллярного рака почки). В исследуемых образцах иммуногистохимически проведена оценка экспрессии маркеров опухолевой стромы, а именно CD68, CD206, PU.1, CD3, IDO1 и PD-L1.Результаты. Анализ общего числа макрофагов, ассоциированных с опухолью, показал, что наименьшее их количество наблюдается в образцах хромофобного рака почки, в то время как в образцах светлоклеточного рака их количество наибольшее. Для Т-клеток отмечена похожая ситуация: наибольшее число CD3+-клеток наблюдается в светлоклеточных опухолях. В хромофобных и папиллярных опухолях их количество снижено. Также папиллярные опухоли характеризуются практически полным отсутствием экспрессии PD-L1 и IDO1 по сравнению с другими гистологическими типами опухолей почки. Также мы показали, что для PU.1 наблюдается сильная положительная корреляция его количества с локализацией, как и для CD68. Таким образом, PU.1 можно использовать в качестве общего маркера для описания стромальных макрофагов в опухолях почки.Заключение. Результаты исследования показали, что опухоли почки различных гистологических типов сильно и значимо отличаются по составу своего микроокружения. Это, несомненно, необходимо учитывать при выборе иммунной терапии в лечении данной патологии

Белки sPD-1/sPD-L1 при немелкоклеточном раке легкого и плоскоклеточном раке пищевода

Background. Implementation of immunotherapy in clinical oncological practice has significantly improved the results of cancer treatment. It resulted in the need for seeking new markers to assess the effectiveness of therapy and the disease prognosis.Aim. To analyze the content of soluble forms of PD-1 and PD-L1 immune checkpoint proteins in the blood serum of patients with non-small cell lung cancer and esophageal squamous cell carcinoma and their association with clinical and morphological characteristics of the disease and the disease prognosis.Materials and methods. The study included tumor samples obtained from 43 patients with non-small cell lung cancer and 21 patients with esophageal squamous cell carcinoma. The concentration of sPD-L1 and sPD-1 in the blood serum was determined using enzyme-linked immunosorbent assay (ELISA). The Mann – Whitney test was used to determine statistically significant differences in independent groups. A correlation analysis was performed using the Spearman’s rank correlation coefficient. Overall survival was analyzed by constructing survival curves using the Kaplan – Meier method and a Cox proportional hazards model. The differences were considered statistically significant at p < 0.05.Results. The study showed that sPD-1 and sPD-L1 were found in the blood serum of both cancer patients and healthy donors, and their concentrations did not differ significantly. It was shown that the high concentration of sPD-L1 in the blood serum of patients with non-small cell lung cancer was significantly associated with the late stage of the disease and was an independent unfavorable prognostic factor. It should be noted that for patients with esophageal cancer, an unfavorable prognostic marker was the high concentration of the soluble form of PD-1 protein, and not PD-L1 ligand, as in case of lung cancer.Conclusion. The content of sPD-1 and sPD-L1 in the blood serum can have different prognostic significance for various types of cancer, and further studies are required to confirm their clinical usability.Введение. Активное внедрение иммунотерапии в клиническую онкологическую практику позволило значительно улучшить результаты лекарственного лечения опухолей. Это привело к необходимости поиска новых маркеров, с помощью которых можно оценить эффективность проводимой терапии и прогноз заболевания.Цель исследования – анализ содержания растворимых форм белков контрольных точек иммунитета sPD-1 и PD-L1 в сыворотке крови больных немелкоклеточным раком легкого и плоскоклеточным раком пищевода, а также их ассоциации с клинико-морфологическими характеристиками заболевания и прогнозом.Материалы и методы. В исследование включены образцы опухолей от 43 пациентов с немелкоклеточным раком легкого и 21 пациента с плоскоклеточным раком пищевода. Концентрацию sPD-L1 и sPD-1 определяли в сыворотке крови с помощью иммуноферментного анализа. Для определения статистически значимых различий в независимых группах использовали критерий Манна – Уитни. Корреляционный анализ проводили с помощью определения коэффициента ранговой корреляции Спирмена. Анализ общей выживаемости – путем построения кривых дожития по методу Каплана – Мейера и с использованием модели пропорциональных рисков Кокса. Статистически достоверными считались различия при р < 0,05.Результаты. Показано, что sPD-1и sPD-L1 обнаруживаются в сыворотке крови как у пациентов с онкологическими заболеваниями, так и здоровых доноров, и их концентрации значимо не отличаются. Показано, что высокая концентрация sPD-L1 в сыворотке крови больных немелкоклеточным раком легкого значимо ассоциирована с поздней стадией заболевания и является независимым неблагоприятным прогностическим фактором. Необходимо отметить, что для пациентов с раком пищевода неблагоприятным прогностическим маркером является высокое содержание растворимой формы рецептора PD-1, а не его лиганда PD-L1, как для рака легкого.Выводы. Содержание в сыворотке крови sPD-1и sPD-L1 может иметь различное прогностическое значение для злокачественных опухолей различных нозологий, и необходимость его анализа для клинического применения требует дальнейшего изучения

TECHNOLOGICAL SYSTEM AND A PARISH COMMUNITY

The article considers the issue of how the Orthodox community as the most traditional social community adapts to the contemporary system of technologies. First, the author describes the phenomenon of technological system, identifies its main features, capabilities and limitations. Among the key features of the technological system, the article focuses on decentralization, weakening hierarchy and strengthening horizontal links, flexibility, self-regulation, adaptability, totality and the use of man as an algorithmically acting subject. The author emphasizes that the system approach in sociology plays an important role in the study of technological systems, and N. Luhmann’s approach is relevant for the study of parish communities, though the author mentions the limitations and critique of his works. The article examines contemporary church discourse about modernization of parish communities, which is also determined by the popularization of the views of Luhmann and other representatives of the system approach. The author also focuses on the most important question of the contemporary world under the technological development, which is the future of the mankind, and the article mentions concepts ‘cyborg’, ‘mutant’, ‘clone’, ‘virtual person’, and ‘posthuman’. The author makes a number of conclusions about how the parish community will react to the changes of the mankind, and what the most possible risks for the parish communities are considering such changes. Thus, the transformation of the parish community into a well-managed and well-functioning system or network means its rationalization, which at first seems necessary and solving urgent problems, but then one can see that it deprives the community of its vitality: a man finds himself in the community, but it does not seem to be Christian any more

Value orientations of the student youth in religious and secular universities

The article presents the results of the factor analysis applied to the data of mass survey on the value orientations of the students of secular and religious universities - Moscow Orthodox Theological Academy and Seminary, Lomonosov Moscow State University and Saint Petersburg State University. First, the authors provide a brief overview of the current state of sociological studies of values and value orientations of the youth and Russians with an emphasis on cross-cultural and other comparative contexts, which are so popular today. The article also considers different emphases in the sociological interpretation of the concepts of values and value orientations on the theoretical and empirical levels including the historical perspective. Since the research project consisted of several stages so as to solve a number of tasks and used different formats of the questionnaire for different samples (administration, professors and students), the article presents only a small part of the project designed to reveal the value orientations of students of secular and religious universities with the help of S. Schwartz and B. Bilski technique. The authors used this technique to identify similarities and differences in values and motives of students of secular and religious universities; suggest four factorial types of motivation; offer an interpretation of the observed factors and their manifestations in different student subsamples, such as the different circumstances of life of students in secular and religious universities and the more “expert” status of the latter in the (Christian, Orthodox) moral discourse, unlike the majority of students of secular universities, who can hardly be considered experts in secular ethics

CHID1 Is a Novel Prognostic Marker of Non-Small Cell Lung Cancer

There is an urgent need for identification of new prognostic markers and therapeutic targets for non-small cell lung cancer (NSCLC). In this study, we evaluated immune cells markers in 100 NSCLC specimens. Immunohistochemical analysis revealed no prognostic value for the markers studied, except CD163 and CD206. At the same time, macrophage markers iNOS and CHID1 were found to be expressed in tumor cells and associated with prognosis. We showed that high iNOS expression is a marker of favorable prognosis for squamous cell lung carcinoma (SCC), and NSCLC in general. Similarly, high CHID1 expression is a marker of good prognosis in adenocarcinoma and in NSCLC in general. Analysis of prognostic significance of a high CHID1/iNOS expression combination showed favorable prognosis with 20 months overall survival of patients from the low CHID1/iNOS expression group. For the first time, we demonstrated that CHID1 can be expressed by NSCLC cells and its high expression is a marker of good prognosis for adenocarcinoma and NSCLC in general. At the same time, high expression of iNOS in tumor cells is a marker of good prognosis in SCC. When used in combination, CHID1 and iNOS show a very good prognostic capacity for NSCLC. We suggest that in the case of lung cancer, tumor-associated macrophages are likely ineffective as a therapeutic target. At the same time, macrophage markers expressed by tumor cells may be considered as targets for anti-tumor therapy or, as in the case of CHID1, as potential anti-tumor agents

Immunosuppressive peculiarities of stromal cells of various kidney tumor types

Background. Renal cell carcinoma is a heterogeneous group of tumors characterized by high vascularization and immunogenicity. Immunotherapy has made a breakthrough in the treatment of this pathology, however, the lack of development of criteria for its use does not allow to achieve even greater success. It is known that the tumor stroma plays an important role in the success of immunotherapy. Among the various histological types of kidney tumors, the stroma of the clear cell renal cell carcinoma has been studied in sufficient detail. However, the remaining histological types are practically not studied.Objective: description of the immunosuppressive phenotype of the stroma of kidney tumors of various histological types.Materials and methods. The study included tumor samples obtainedfrom 44patients with renal cell carcinoma of various histological types (16 samples of chromophobe cancer, 15 samples of clear cell and 13 samples of papillary renal cell carcinoma). The method of immunohis-tochemistry evaluated the expression of tumor stromal markers, namely CD68, CD206, PU.1, CD3, IDO1 and PD-L1 in the studied samples.Results. Analysis of the total number of macrophages associated with the tumor showed that the smallest number is observed in samples of chromophobe renal cancer, while in the samples of clear cell cancer their number is greatest. A similar situation is observed for T-cells: the largest number of CD3+ cells is observed in clear cell tumors. In chromophobe and papillary tumors, their number is reduced. Papillary tumors are also characterized by an almost complete absence of expression of PD-L1 and IDO1 compared to other histological types of kidney tumors. We also showed that for PU.1 there is a strong positive correlation between its quantity and localization, as in CD68. Thus, PU.1 can be used as a general marker for describing stromal macrophages in kidney tumors.Conclusion. The study showed that kidney tumors of various histological types strongly and significantly differ in the composition of their microenvironment. These data, of course, must be considered when choosing immune therapy in the treatment of this pathology

Gd3+-Doped Magnetic Nanoparticles for Biomedical Applications

Magnetic nanoparticles (MNPs) made of iron oxides with cubic symmetry (Fe3O4, γ-Fe2O3) are demanded objects for multipurpose in biomedical applications as contrast agents for magnetic resonance imaging, magnetically driven carriers for drug delivery, and heaters in hyperthermia cancer treatment. An optimum balance between the right particle size and good magnetic response can be reached by a selection of a synthesis method and by doping with rare earth elements. Here, we present a microwave-assisted polyol synthesis of iron oxide MNPs with actual gadolinium (III) doping from 0.5 to 5.1 mol.%. The resulting MNPs have an average size of 14 nm with narrow size distribution. Their surface was covered by a glycol layer, which prevents aggregation and improves biocompatibility. The magnetic hyperthermia test was performed on 1 and 2 mg/ml aqueous colloidal solutions of MNPs and demonstrated their ability to rise the temperature by 3°C during a 20–30 min run. Therefore, the obtained Gd3+ MNPs are the promising material for biomedicine