85 research outputs found
230303_JID_3708_FilippFV_02_high_resolution.jpg
No full textSpatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event; Author; Fabian V Filipp;
https://doi.org/10.1016/j.jid.2023.02.006;
https://doi.org/10.1101/2023.03.01.530706; https://doi.org/10.48550/arXiv.2303.00933; orcid.org/0000-0001-9889-5727; https://www.jidonline.org;
Figure Legend: WNT-ligand (WNT) and cognate frizzled (FZD) receptor gene expression network in skin cutaneous melanoma
(a) Disruption of heterotypic signaling in skin cutaneous melanoma (SKCM) RNA-Seq gene expression and differential gene expression (ΔRNA-Seq) values in reads per kilobase million between metastatic tumor (TM) and primary tumor (TP) in patient biopsies of The Cancer Genome Atlas (TCGA). Heterotypic signaling in tissue development includes interactions between different cell types. In disease, such interaction networks are rewired, resulting in heterotypic interactions between cancer cells and immune or stromal components. In addition, hyperplastic malignant cells may exhibit homotypic interactions, by expressing ligand and cognate receptor on the same cell type. (b) Heterotypic cell-cell communication in tissue organization such as planar cell polarity requires interaction of a specific WNT-ligand with their cognate frizzled (FZD) receptor. The sequence identity matrix highlights evolutionary conservation between homologs. An unsupervised clustering tree in combination with multiple sequence alignments across 19 WNT and 10 FZD protein isoforms identifies molecular specificity and redundancy in the heterotypic signaling network.</p
Representation of health as a subject of psychological researches
No full textIn this article the author describes a long-term comprehensive study of various forms of social and individual health representation in a youth (student) social group. A theoretical analysis of various approaches to understanding the phenomenon of health, developed in the framework of social medicine, clinical psychology, a psychosomatic school, behavioral and cognitive areas of psychology and psychotherapy, humanistic personality theories, is carried out. Different levels of conceptualization of the health phenomenon are considered (as a socio-cultural / semantic construct and as a significant aspect of an individual self-concept). The author analyzes the theoretical foundations and scientific specifics of the Health psychology, as an independent field of psychological knowledge. The author also analyzes the results of a comprehensive study of the “internal representation of health” that was formed among junior students of natural sciences and humanities departments at the Russian State University. Specific types of the internal representation of health are revealed and described
«The mission of the russian intelligentsia» in the works of Lev Tikhomirov
No full textThis paper is devoted to the work of political activist and writer Lev Alexandrovich Tikhomirov. Considered and reviewed diaries, memoirs and journalism Tikhomirov, reflecting the two periods of his life: while promoting the ideology of the party «People’s Freedom» («Narodnaya Volya») and service to the monarchical idea. The author shows that the main factor that influenced the development of creativity Lev Tikhomirov as a populist, and the monarchical period, was the conviction of the special mission of the Russian intelligentsia in Russian history
The Time and Reasons for Fyodor Kolychev’s Retreat to the Solovetsky Monastery
No full textThe article was submitted on 09.02.2021.Рассматривается первый этап жизни митрополита Филиппа (в миру – Федора Степановича Колычева, 1566–1568). Автор сосредотачивается на изучении мотивов и обстоятельств его ухода в Соловецкий монастырь. В работе оспаривается распространенная в литературе гипотеза о том, что уход Филиппа был напрямую связан с репрессиями против Колычевых после подавления Старицкого мятежа в 1537 г. Показано, что, во-первых, непосредственно семья Степана Колычева репрессиям не подверглась, во-вторых, уход Федора на Соловки состоялся до Старицкого мятежа – в первой половине 1534 г. К этому времени он уже был зрелым по меркам Средневековья 27-летним человеком. Автор приходит к выводу о добровольности и осознанности решения Федора об уходе в монастырь. Устанавливается, что причины этого шага следует искать не в политической сфере, а исключительно в сфере религиозного сознания. К моменту пострига нереализованных политический амбиций у Филиппа не осталось. Это отличало его от Вассиана (Патрикеева) и Филарета (Романова), вынужденно принявших постриг и порой рассматривавших церковную сферу как поле для удовлетворения своего честолюбия. «Социальный капитал», которым располагал Филипп к моменту пострига, мог сыграть важную роль в его избрании в игумены Соловецкого монастыря. Его иноки нуждались в относительно молодом и энергичном настоятеле, который располагал навыками и опытом управления крупным хозяйством. 37–38-летнего Филиппа отличала приобретенная в миру хозяйственная хватка, а иных иноков из среды служилых людей в этой обители в этот период было немного. Избрание Филиппа в игумены во многом предопределило расцвет вотчины Соловецкого монастыря в 1540–1560-е гг. В основу исследования положены летописные и актовые источники, записи на книгах, а также Житие митрополита Филиппа. Их изучение ведется с применением методов источниковедческого анализа, позволяющих из отрывочных и порой разноречивых показаний источников воссоздать картину прошлого. Особое внимание уделено анализу текста жития Филиппа, давшего возможность отделить представленные в нем ценные сведения о биографии митрополита от основного текста, написанного с обильным использованием агиографической топики.This article considers the first stage of the life of Metropolitan Filipp (lay name Fyodor Stepanovich Kolychev, 1566–1568). The author focuses on the motives and circumstances of his retreat to the Solovetsky monastery. The work calls into question the widespread hypothesis according to which his joining the monastery was closely connected with the repression against the Kolychevs after the suppression of the Staritsky mutiny in 1537. The author demonstrates that, firstly, Stepan Kolychev’s family was not persecuted and, secondly, that Fyodor had gone to the Solovetsky Islands before the Staritsky mutiny took place, i. e. in the first half of 1534. By that time, he was a mature twenty-seven- year-old (by the standards of the time). The author comes to conclusion that Fyodor decided to enter the monastery consciously and voluntarily. The reasons for his decision should not be sought in the political sphere but only in the sphere of religious consciousness. By the moment of taking his monastic vows, he had no unrealised political ambitions left. This fact distinguishes him from Vassian (Patrikeev) and Filaret (Romanov), who were forced to take monastic vows and regarded the Church as the sphere where they could realise their ambitions. Fyodor’s social skills may have played a very important role in him being elected abbot of the Solovetsky monastery. The monks needed a young and active abbot who would have the skills and experience to manage a large household. At 37–38 years of age, Filipp had business acumen, and not so many monks came from the service class. The election of Filipp contributed to the flourishing of the Solovetsky monastery’s patrimony in the 1540s–1560s. The research refers to chronicles, acts, colophons, and the Life of Metropolitan Filipp. These historical sources are analysed with the help of source study methods, which make it possible to reconstruct the past from contradictory and fragmentary evidence. The author pays much attention to the analysis of Filipp’s Life and tries to distinguish valuable facts of his biography from typical hagiographic motifs
Methoden zur Beschreibung von chemischen Strukturen beliebiger Dimensionalität mit der Dichtefunktionaltheorie unter periodischen Randbedingungen
No full textDie vorliegende Arbeit ist ein Beitrag auf dem Gebiet der theoretischen Chemie und beschäftigt sich mit der Entwicklung effizienter Berechnungsmethoden für die Elektronendichte und die Energie des Grundzustands molekularer und periodischer Systeme im Rahmen der Kohn-Sham-Dichtefunktionaltheorie (Kohn-Sham-DFT) und unter Verwendung von lokalen Basisfunktionen. Im Vordergrund steht dabei die einheitliche Beschreibung von Molekülen und ausgedehnten Systemen beliebiger Periodizität (zum Beispiel Volumenkristalle, dünne Filme und Polymere) mit einfachen Algorithmen bei einem hohen Maß an numerischer Genauigkeit und Recheneffizienz. Dafür hat der Verfasser bewährte molekulare Simulationsmethoden in neuartiger Form auf periodische Randbedingungen erweitert und zu einer vollständigen DFT-Methode vereint. Von diesen Methoden ist das völlig neue Konzept für die RI-Methode (resolution of identity, Zerlegung der Einheit), die auf den Coulomb-Term angewendet wird, die Schlüsseltechnologie in dieser Arbeit. Ein Merkmal der Methode ist, dass sie ausschließlich im direkten Raum arbeitet. Neben der RI-Methode wurden weitere methodische Ansätze entwickelt werden, um eine gute Speicher- und Zeiteffizienz der gesamten DFT-Methode zu gewährleisten. Dazu gehören die Komprimierung der speicherintensiven Dichte- und Kohn-Sham-Matrizes und die numerische Integration des Austausch-Korrelationsterms durch die Anwendung eines adaptiven, numerischen Integrationsschemas. Die vorgestellten Methoden werden zum Prototypen eines RI-DFT-Programms zusammengefügt. Dieses Programm ermöglicht die Berechnung von single point-Energien am Gamma-Punkt für Systeme mit abgeschlossenen Schalen. Anhand von Berechnungen werden die numerische Genauigkeit und Effizienz bewertet. Das Programm bildet die Basis für ein effizientes und leistungsfähiges DFT-Programm, das Moleküle und periodische Systeme methodisch einheitlich und numerisch genau behandelt.This work contributes to the field of theoretical chemistry and is aimed at the development of efficient methods for computation of the electron density and the energy belonging to the ground state of molecular and periodic systems. It is based on the use of Kohn Sham density functional theory (Kohn Sham DFT) and local basis functions. In this scope, the molecular and the periodic systems of any dimensionality (e.g., bulk crystals, thin films, and polymers) are treated on an equal footing using methods which are easy to implement, numerically accurate, and highly efficient. For this, the author has augmented established methods of molecular simulations for their use with periodic boundary conditions applying novel techniques. These methods have been combined to a complete DFT method. Among these methods, the innovative approach for the RI (resolution of identity) method applied to the Coulomb term represents the key technology of this work. As a striking feature, this approach operates exclusively in real space. Although the RI method is the chief ingredient, the development of further methods is required to achieve overall efficiency for the consumption of storage and time. One of these methods is used to compress the density and Kohn Sham matrices. Moreover, numerical integration of the exchange-correlation term has been improved applying an adaptive numerical integration scheme. The methods presented in this thesis are combined to the prototype of an RI-DFT program. Using this program single point energies on the gamma point can be calculated for systems with closed shells. Calculations have been performed and the results are used to assess the accuracy and efficiency achieved. This program forms the foundation of an efficient and competitive DFT code. It works numerically accurate and treats molecules and periodic systems on an equal footing
Robustness of Neural Ratio and Posterior Estimators to Distributional Shifts for Population-level Dark Matter Analysis in Strong Gravitational Lensing
No full textWe investigate the robustness of neural ratio estimators (NREs) and sequential neural posterior estimators (SNPEs) to distributional shifts in the context of measuring the abundance of dark matter subhalos using strong gravitational lensing data. While these data-driven inference frameworks can be accurate on test data from the same distribution as the training sets, in real applications, it is expected that simulated training data and true observational data will differ in their distributions. We explore the behavior of a trained NRE and trained SNPEs to estimate the population-level parameters of dark matter subhalos from a large sample of images of strongly lensed galaxies with test data presenting distributional shifts within and beyond the bounds of the training distribution in the nuisance parameters (e.g., the background source morphology). While our results show that NREs and SNPEs perform well when tested perfectly in distribution, they exhibit significant biases that often lead to not recovering the ground truth in the 3 σ interval when confronted with slight deviations from the examples seen in the training distribution. This indicates the necessity for caution when applying NREs and SNPEs to real astrophysical data, where high-dimensional underlying distributions are not perfectly known
Is There an “Acquired Idiopathic Head-Shaking Nystagmus”?—A Discussion of Mechanisms and Clinical Implications Based on a Case Report
No full textBACKGROUND: Head-shaking nystagmus (HSN) occurs in both peripheral and central vestibular disorders. In most cases, HSN can be attributed to an asymmetric peripheral vestibular input or a structural lesion mostly in the cerebellum affecting the central velocity storage mechanism. An isolated HSN is very rare. CASE PRESENTATION: We report on a young female patient with the clinical picture of recurrent episodes of vertigo, which were induced by fast head movements and were accompanied by a severe right-beating HSN with a long time constant of 60 s. There was no other clinical and instrument-based evidence of peripheral vestibular dysfunction (including video head impulse test, caloric test, vestibular-evoked myogenic potentials) or indication of a structural lesion in the nodulus, uvula or pontomedullary brainstem on fine-slice magnetic resonance imaging. She had no previous history of migraine, hearing deficits, or other focal neurological symptoms. Diagnostic criteria for vestibular paroxysmia, vestibular migraine, benign peripheral paroxysmal vertigo, or any other known vestibular disorders were not fulfilled. Chart review in the database of the German Center for Vertigo and Balance Disorders indicated eight additional patients with a similar clinical phenotype between 2018 and 2022. CONCLUSION: We propose a clinical entity called acquired idiopathic head shaking nystagmus (aiHSN) as a rare cause of episodic vertigo induced by fast head movements. Nystagmus characteristics suggest a subtle functional pathology of the central velocity storage mechanism in the nodulus and uvula, which is exacerbated during symptomatic episodes
Surface structure and physicomechanical properties of NiTi exposed to electron beam and ion-plasma treatment
No full textПерспективы развития праворадикального движения в Европе
No full textНа сегодняшний день праворадикальные лозунги слышатся все чаще и чаще, от туманного Альбиона до восточных границ Европы. Интерес к национальному государству постепенно возрождается, учитывая неиссякаемый поток проблем, с которыми сталкивается сегодняшняя Европа. Вопросы нации и национализма становятся одними из самых главных и значимых для многих европейских государств, в первую очередь – западных. Праворадикальные националисты занимают особое место в партийно-политическом спектре современных западноевропейских сообществ. Они принципиально отличаются от традиционных консервативных и неоконсервативных партий. Последние, даже разделяя ряд националистических постулатов, никогда не ставят под сомнение основополагающие ценности либеральной демократии. В настоящей статье автор анализирует феномен электоральной популярности праворадикальных партий в современной Европе, а также историю становления крайне правых партий как влиятельного актора политического процесса и особенности эволюции их идеологического дискурса. Кроме того, в совокупности будут приведены ключевые аспекты политических программ некоторых европейских праворадикальных партий, выявлены их сходные и различные парадигмы и аспекты.Today the right-wing slogans are heard more and more often, from Albion to the eastern borders of Europe. Interest in the nation-state is gradually being revived, given the endless stream of problems facing today's Europe. Questions of nation and nationalism are among the most important and relevant for many European countries, first of all - the Western. Right-wing nationalists have a special place in the party-political spectrum of modern Western societies. They are fundamentally different from the traditional conservative and neoconservative parties. They [neoconservative parties] even sharing a number of nationalist tenets, never questioned the fundamental values of liberal democracy. In this article the author analyzes the phenomenon of electoral popularity of radical right parties in modern Europe, as well as the history of the formation of far-right parties as an influential actor in the political process and the evolution of their ideological discourse. In addition, the aggregate will be given the key aspects of the political programs of some European right-wing parties, found their similar and different paradigms and aspects
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