18 research outputs found
Connecting instructional and cognitive aspects of an LE: A study of the global seminar project
No full textMy research problem is based on the lack of unifying conceptual cohesion between the discourses concerning cognitive and instructional aspects of learning environments (LE). I contrast that lack with practical developments of LE studies connected at the level of practical implementation and evaluation. Next, I briefly review the LE boundaries, which are established within cognitive and instructional domains of LE research. This study aims to bring the aforementioned discourses together via reconsidering and clarifying LE conceptual understandings. Using the case of a global seminar project (GSP), my goal is to define an LE as a conceptual phenomenon and a practical model with the two objectives of determining the GSP's components that establish the course in a context of higher education; and the GSP's specific contributions to deep learning. Within a qualitative research framework, I used three forms of data collection: 20 open-ended interviews of the GSP instructors; 11 direct observations of the GSP classroom; and the GSP's written documents and artifacts. Noting the contextual significance of the suggested LE framework that resulted from this study, I propose a definition of an LE as a conceptual phenomenon and educational model. Here, I introduce the key understandings of an LE and outline its significance based on a broader analysis of the results. I conclude with an interpretation of the results and potential limitations of my approach. © 2012 The Author(s).published_or_final_versionSpringer Open Choice, 28 May 201
In these (end) times: Sh. Idiatullin's Volgaic fantasy fiction
No full textThe paper discusses the development of ethnic fiction in the modern Russian literature, focusing on Shamil Idiatullin's 2020 novel “Poslednee vremja”. We show that the tendency towards switching from ethnic to regionalist agenda can be observed in the works by both Russian authors, such as Denis Osokin and Alexei Ivanov, and authors having a non-Russian ethnic identity, such as the Tatar novelists Guzel Yakhina and Shamil Idiatullin. We adopt an interdisciplinary approach, bringing together techniques from literary studies (analysis of the genre and the literary situation as well as the historical and cultural context) and linguistics (an etymological analysis of proper names, in the first place). Our commentary on various linguistic, historical and cultural aspects puts Idiatullin»s novel into the discourse of the contemporary ethnic fiction as a text that expresses the positions of both the Conquerors and the Conquered. The analysis of personal names and other words of non-Russian origin that are used in the Russian text allows to identify the fictional ethnic groups with the actual peoples of the Volga-Kama region and places the novel within a present-day context. One of the key themes of “Poslednee vremja” is language loss, and some scenes, such as the self-immolation of the pagan priest Arβuj-Kuγə̑za, make a clear reference to the contemporary history of the region. The novel»s title can be translated as both “End times” and “These times”; thus, it includes simultaneously an apocalyptic allusion and a hint to the events of the recent past
Monuments of old Russian lexicography in the manuscript of Prokhor Kolomnyatin
No full textThe article describes the monuments of Old Russian lexicography recorded in a manuscript created in 1668 by monk Prokhor Kolomnyatin, a Russian teacher and lexicographer. The dictionary “Tolkovanie o psaltyrnykh slovesekh” (‘Interpretation of the Psalms’), following a well-known tradition represented by numerous copies, could have been borrowed by the author from the Moscow edition of the Psaltyr of 1641. The dictionary “Latinskie rechi” (‘Latin Words’) is a translation of the Latin-Greek dictionary attributed to Matthew Blastares and included in his “Sintagma” (‘Syntagma’); one of the Slavic copies of this book served as a source for a Latin dictionary in the manuscript of 1668. The third text, “Perevodnye rechi s grecheskogo yazyka na slovenskii” (‘Translated Words from Greek into Slovenian’), is a Greek-Russian dictionary which is built on a thematic principle. This monument is based on the materials of the azbukovniks (‘alphabet books’), as well as the words and phrases of “Rech’ tonkosloviya grecheskogo” (‘Words of Greek Subtlety’), which were borrowed by Prokhor Kolomnyatin from “Vtoroi azbukovnik” (‘The Second Alphabet Book’). In the division of the lexical material into thematic groups, one can assume the influence of the works of Jan Amos Comenius. Although the work on compiling the Greek-Russian dictionary remained unfinished, it was the principle of its construction that served as a model for the recording of three new phrasebook dictionaries created by Prokhor Kolomnyatin
IL-4 enhances expression and function of surface IgM in CLL cells
No full textKinase-inhibitors targeting the B-cell receptor (BCR) are now prominent in the treatment of CLL. We have focused here on IL-4, a cytokine which protects normal and malignant B cells from apoptosis, and increases surface (s)IgM expression on murine splenic B cells. First we have demonstrated that IL-4 treatment increased sIgM expression in vitro on peripheral blood B cells obtained from healthy individuals. In CLL, IL-4 target genes are overexpressed in cells purified from the lymph nodes of patients compared to cells derived from matched blood and bone marrow samples. As for normal B cells, IL-4 increased sIgM expression on CLL cells in vitro, especially in samples expressing unmutated V-genes (U-CLL). IL-4-induced sIgM expression was associated with increased receptor signalling activity, measured by anti-IgM-induced calcium mobilisation, and with increased expression of CD79B mRNA and protein, and the "mature" glycoform of sIgM. Importantly, the ability of the BCR-associated kinase inhibitors idelalisib and ibrutinib, approved for treatment of CLL and other B-cell malignancies, to inhibit anti-IgM-induced signalling was reduced following IL-4 pre-treatment in samples from the majority of patients. In contrast to stimulatory effects on sIgM, IL-4 decreased CXCR4 and CXCR5 expression. Therefore CLL cells, particularly within the progressive U-CLL subset, may harness the ability of IL-4 to promote BCR signalling and B-cell retention within lymph nodes. Effects of IL-4 were mediated via JAK3/STAT6 and we propose a potential role for JAK inhibitors in combination with BCR-kinase inhibitors for the treatment of CLL
Methodological aspects of building the indicator for revealing distortions in company results
No full textToday it is extremely timely and acute to stir up academic quarters in order to develop methodological basis for assessing the degree of accounts trustworthiness in the interest of all groups of company stakeholders. The article studies theoretical and methodological aspects of assessing accounts manipulation. The author came to the conclusion about availability of shortcomings in the effective tools of assessing accounts manipulation, which are connected with determinism of indicators included in their structure and ignoring specificity of different types of company activity. The article proposes a new approach to probabilistic assessment of distortions in company accounts, which leans on mathematic-statistic models, namely typologization and multi-criteria estimation. This approach makes it feasible not only to find facts of accounts distortion but to identify their trend in the direction of overstating or understating. On the basis of this approach the integral indicator of assessing possibility of finance results’ distortion in company accounting in the direction of their overstating was built. It is connected with companies, whose principle type of activity is food production. The author draws a conclusion that more than a half of joint stock companies in the Russian Federation dealing with food production provide untruthful finance accounting (with the possibility of over 60%), which overstates finance results of its work
Assessing successful reproduction of egocentric and allocentric spatial representations using virtual reality
No full textBackground. Currently in psychological rehabilitation the necessity of developing innovative methods for testing cognitive dysfunctions with via the modern sophisticated technology is becoming increasingly important. One of the urgent requests is associated with developing the methods of diagnostics and correction of spatial representations disorders, which are manifested by decreasing accuracy of spatial representations of the environment in particular.
Objective. To study this issue the method for evaluating the accuracy of spatial information using which the ability to memorize the three-dimensional complex scenes was developed. It was assumed that the accuracy of reproduction would differ significantly depending on the coordinate (egocentric or allocentric) system of mental reconstruction processing.
Design. The library of virtual objects and six unique virtual scenes were created. Each scene of seven objects was shown to the participants within the interval for 25 seconds. Thirty six subjects (aged from 18 to 26) participated in the experiment. They were told to memorize the objects and their locations, and then to reproduce the memorized scene using the given viewpoint of the scene. Three viewpoints were chosen: the «front» (to reproduce the scene from the egocentric position); the «left» and the» above» (to reproduce the memorized scene from on the left and above imaginary allocentric positions, respectively). To perform the task the participants chose objects from the library of virtual objects using the flystick 2 and placed them in virtual space in accordance with the memorized scene. The object locations in virtual space were recorded. Moreover, the accuracy of egocentric and allocentric representations in terms of measurements, topology and depth parameters were calculated.
Conclusion. The results show that the egocentric representations (the «front» viewpoint) were more accurate for all parameters in comparison with the allocentric representations (the «left» and the «above» viewpoints), and the “above” representations were more accurate compared with the “left” ones. The topological accuracy was much better than the measurements and depth accuracy. Regardless of the viewpoints, the topological space parameters are stored in memory much more accurately than the depth parameters, which, in turn, are reproduced more accurately than metric parameters. It was also shown that the accuracy of spatial representations differs for different allocentric viewpoints: the «above» view is reproduced much more accurately than the «left» view. The method developed made it possible to reveal the features of encoding spatial information in ER and AP blocks in terms of measurements, topology and depth parameters. It can be used in clinical rehabilitation to test impairments in the perception of space, and also violations of short-term memory. The results obtained allow refining the existing models of encoding spatial information
Security of the state power limits: limit system
No full textThe article discusses the limitations of state power, presented in the form of a backbone foundation, constructed on the foundation of a methodologically significant classification basis: a place in the social regulation system. In the context of the stated perspective, the author builds up a set of limitations of the axiological level, which appears to be determined in the field of public relation
Bioelectronic microfluidic wound healing: a platform for investigating direct current stimulation of injured cell collectives
No full textUpon cutaneous injury, the human body naturally forms an electric field (EF) that acts as a guidance cue for relevant cellular and tissue repair and reorganization. However, the direct current (DC) flow imparted by this EF can be impacted by a variety of diseases. This work delves into the impact of DC stimulation on both healthy and diabetic in vitro wound healing models of human keratinocytes, the most prevalent cell type of the skin. The culmination of non-metal electrode materials and prudent microfluidic design allowed us to create a compact bioelectronic platform to study the effects of different sustained (12 hours galvanostatic DC) EF configurations on wound closure dynamics. Specifically, we compared if electrotactically closing a wound&apos;s gap from one wound edge (i.e., uni-directional EF) is as effective as compared to alternatingly polarizing both the wound&apos;s edges (i.e., pseudo-converging EF) as both of these spatial stimulation strategies are fundamental to the eventual translational electrode design and strategy. We found that uni-directional electric guidance cues were superior in group keratinocyte healing dynamics by enhancing the wound closure rate nearly three-fold for both healthy and diabetic-like keratinocyte collectives, compared to their non-stimulated respective controls. The motility-inhibited and diabetic-like keratinocytes regained wound closure rates with uni-directional electrical stimulation (increase from 1.0 to 2.8% h−1) comparable to their healthy non-stimulated keratinocyte counterparts (3.5% h−1). Our results bring hope that electrical stimulation delivered in a controlled manner can be a viable pathway to accelerate wound repair, and also by providing a baseline for other researchers trying to find an optimal electrode blueprint for in vivo DC stimulation.Validerad;2023;Nivå 2;2023-04-18 (joosat);Funder: German Research Foundation, DFG ( EXC 1086); Federal Ministry of Economics, Science and Arts of Baden Württemberg; Wissenschaftliche Gesellschaft Freiburg; Deutscher Akademischer AustauschdienstLicens fulltext: CC BY License</p
ATM regulates differentiation of myofibroblastic cancer-associated fibroblasts and can be targeted to overcome immunotherapy resistance
No full textMyofibroblastic cancer-associated fibroblast (myoCAF)-rich tumors generally contain few T cells and respond poorly to immune-checkpoint blockade. Although myoCAFs are associated with poor outcome in most solid tumors, the molecular mechanisms regulating myoCAF accumulation remain unclear, limiting the potential for therapeutic intervention. Here, we identify ataxia-telangiectasia mutated (ATM) as a central regulator of the myoCAF phenotype. Differentiating myofibroblasts in vitro and myoCAFs cultured ex vivo display activated ATM signaling, and targeting ATM genetically or pharmacologically could suppress and reverse differentiation. ATM activation was regulated by the reactive oxygen species-producing enzyme NOX4, both through DNA damage and increased oxidative stress. Targeting fibroblast ATM in vivo suppressed myoCAF-rich tumor growth, promoted intratumoral CD8 T-cell infiltration, and potentiated the response to anti-PD-1 blockade and antitumor vaccination. This work identifies a novel pathway regulating myoCAF differentiation and provides a rationale for using ATM inhibitors to overcome CAF-mediated immunotherapy resistance. SIGNIFICANCE: ATM signaling supports the differentiation of myoCAFs to suppress T-cell infiltration and antitumor immunity, supporting the potential clinical use of ATM inhibitors in combination with checkpoint inhibition in myoCAF-rich, immune-cold tumors.</p
Effects of BRCA2 cis-regulation in normal breast and cancer risk amongst BRCA2 mutation carriers
No full text<p>Introduction: Cis-acting regulatory single nucleotide polymorphisms (SNPs) at specific loci may modulate penetrance of germline mutations at the same loci by introducing different levels of expression of the wild-type allele. We have previously reported that BRCA2 shows differential allelic expression and we hypothesize that the known variable penetrance of BRCA2 mutations might be associated with this mechanism.</p>
<p>Methods: We combined haplotype analysis and differential allelic expression of BRCA2 in breast tissue to identify expression haplotypes and candidate cis-regulatory variants. These candidate variants underwent selection based on in silico predictions for regulatory potential and disruption of transcription factor binding, and were functionally analyzed in vitro and in vivo in normal and breast cancer cell lines. SNPs tagging the expression haplotypes were correlated with the total expression of several genes in breast tissue measured by Taqman and microarray technologies. The effect of the expression haplotypes on breast cancer risk in BRCA2 mutation carriers was investigated in 2,754 carriers.</p>
<p>Results: We identified common haplotypes associated with differences in the levels of BRCA2 expression in human breast cells. We characterized three cis-regulatory SNPs located at the promoter and two intronic regulatory elements which affect the binding of the transcription factors C/EBPα, HMGA1, D-binding protein (DBP) and ZF5. We showed that the expression haplotypes also correlated with changes in the expression of other genes in normal breast. Furthermore, there was suggestive evidence that the minor allele of SNP rs4942440, which is associated with higher BRCA2 expression, is also associated with a reduced risk of breast cancer (per-allele hazard ratio (HR) = 0.85, 95% confidence interval (CI) = 0.72 to 1.00, P-trend = 0.048).</p>
<p>Conclusions: Our work provides further insights into the role of cis-regulatory variation in the penetrance of disease-causing mutations. We identified small-effect genetic variants associated with allelic expression differences in BRCA2 which could possibly affect the risk in mutation carriers through altering expression levels of the wild-type allele.</p>
