Expanding on a quinazoline scaffold, we developed tricyclic compounds with biological activity. These compounds bind to the 18 kDa translocator protein (TSPO) and protect U118MG (glioblastoma cell line of glial origin) cells from glutamate-induced cell death. Fascinating, they can induce neuronal differentiation of PC12 cells (cell line of pheochromocytoma origin with neuronal characteristics) known to display neuronal characteristics, including outgrowth of neurites, tubulin expression, and NeuN (antigen known as ‘neuronal nuclei’, also known as Rbfox3) expression. As part of the neurodifferentiation process, they can amplify cell death induced by glutamate. Interestingly, the compound 2-phenylquinazolin-4-yl dimethylcarbamate (MGV-1) can induce expansive neurite sprouting on its own and also in synergy with nerve growth factor and with glutamate. Glycine is not required, indicating that N-methyl-D-aspartate receptors are not involved in this activity. These diverse effects on cells of glial origin and on cells with neuronal characteristics induced in culture by this one compound, MGV-1, as reported in this article, mimic the diverse events that take place during embryonic development of the brain (maintenance of glial integrity, differentiation of progenitor cells to mature neurons, and weeding out of non-differentiating progenitor cells). Such mechanisms are also important for protective, curative, and restorative processes that occur during and after brain injury and brain disease. Indeed, we found in a rat model of systemic kainic acid injection that MGV-1 can prevent seizures, counteract the process of ongoing brain damage, including edema, and restore behavior defects to normal patterns. Furthermore, in the R6-2 (transgenic mouse model for Huntington disease; Strain name: B6CBA-Tg(HDexon1)62Gpb/3J) transgenic mouse model for Huntington disease, derivatives of MGV-1 can increase lifespan by >20% and reduce incidence of abnormal movements. Also in vitro, these derivatives were more effective than MGV-1.
Expanding on a quinazoline scaffold, we developed tricyclic compounds with biological activity. These compounds bind to the 18 kDa translocator protein (TSPO) and protect U118MG (glioblastoma cell line of glial origin) cells from glutamate-induced cell death. Fascinating, they can induce neuronal differentiation of PC12 cells (cell line of pheochromocytoma origin with neuronal characteristics) known to display neuronal characteristics, including outgrowth of neurites, tubulin expression, and NeuN (antigen known as ‘neuronal nuclei’, also known as Rbfox3) expression. As part of the neurodifferentiation process, they can amplify cell death induced by glutamate. Interestingly, the compound 2-phenylquinazolin-4-yl dimethylcarbamate (MGV-1) can induce expansive neurite sprouting on its own and also in synergy with nerve growth factor and with glutamate. Glycine is not required, indicating that N-methyl-D-aspartate receptors are not involved in this activity. These diverse effects on cells of glial origin and on cells with neuronal characteristics induced in culture by this one compound, MGV-1, as reported in this article, mimic the diverse events that take place during embryonic development of the brain (maintenance of glial integrity, differentiation of progenitor cells to mature neurons, and weeding out of non-differentiating progenitor cells). Such mechanisms are also important for protective, curative, and restorative processes that occur during and after brain injury and brain disease. Indeed, we found in a rat model of systemic kainic acid injection that MGV-1 can prevent seizures, counteract the process of ongoing brain damage, including edema, and restore behavior defects to normal patterns. Furthermore, in the R6-2 (transgenic mouse model for Huntington disease; Strain name: B6CBA-Tg(HDexon1)62Gpb/3J) transgenic mouse model for Huntington disease, derivatives of MGV-1 can increase lifespan by >20% and reduce incidence of abnormal movements. Also in vitro, these derivatives were more effective than MGV-1.
The paper focuses on the four “pedagogical” novels by writer and journalist Frida Vigdorova, mostly known for her records of the Joseph Brodsky’s trial of 1964. These novels written in 1949–1958, as well as some of her journalistic publications of the 1950s, made her one of the most influential publicists who wrote on the problems of school and schoolchildren. The article traces Vigdorova’s key ideas and literary techniques back to the second half of 1940s, when she wrote her first novels, first and foremost My Class (1949). Although Vigdorova was regarded as a follower of Anton Makarenko, the famous pedagogue of the 1920s and 1930s, one may find a significant shift in her interpretation of his theory. The main difference consists in her emphasis on the idea of the “individual approach” to each child, by contrast to the earlier attention to the issues of the collective. This idea is represented as a strong moral demand on every teacher or educator. The author shows that this idea was “re-invented” in the late 1940s by the officials of the ministry of education and pedagogical publicists in order to respond to a strong pressure of the pedagogical corps that had to face severe problems that emerged as direct social effects of WWII and were exacerbated by the banning of all psychological approaches to children after 1936. The “individual approach” becomes not only an ideological, but also a literary basis of all Vigdorova’s novels, a structural principle of her narratives.
January 2015: Maria Mayofis is an Associate Professor and Senior Research Fellow at the School of Advanced Studies for Humanities, Russian Academy of National Economy and Public Administration, Moscow. She is the author of several works on Russian history and culture of the late 18th – early 19th centuries, including a monograph Appeal to Europe: “Arzamas” Literary Society and Russian Modernization Project of 1815-1818 (Moscow, 2008). She has co-authored several volumes and edited collections of articles on the history of childhood and children’s culture in the late USSR and Post-Soviet Russia, such as Vesiolye chelovechki: kulturnye geroi sovetskogo detstva (Moscow, 2008). She is currently working on a series of articles devoted to the history of Soviet education.
Background: Schizophrenia is a severe and chronic medical condition, characterized by positive and negative symptoms, as well as pervasive social cognitive deficits. Despite the functional significance of the social cognition deficits affecting many aspects of daily living, such as social relationships, occupational status, and independent living, there is still no effective treatment option for these deficits, which is applied as standard of care. To address this need, we developed a novel, internet-based training program that targets social cognition deficits in schizophrenia (SocialVille). Preliminary studies demonstrate the feasibility and initial efficacy of Socialville in schizophrenia patients (Nahum et al., 2014). The purpose of the current trial (referred to as the TReatment of Social cognition in Schizophrenia Trial or TRuSST) is to compare SocialVille to an active control training condition, include a larger sample of patients, and assess both social cognitive functioning,
The physics of interacting integer-spin chains has been a topic of intense theoretical interest, particularly in the context of symmetry-protected topological phases. However, there has not been a controllable model system to study this physics experimentally. We demonstrate how spin-dependent forces on trapped ions can be used to engineer an effective system of interacting spin-1 particles. Our system evolves coherently under an applied spin-1 XY Hamiltonian with tunable, long-range couplings, and all three quantum levels at each site participate in the dynamics. We observe the time evolution of the system and verify its coherence by entangling a pair of effective three-level particles (“qutrits”) with 86% fidelity. By adiabatically ramping a global field, we produce ground states of the XY model, and we demonstrate an instance where the ground state cannot be created without breaking the same symmetries that protect the topological Haldane phase. This experimental platform enables future studies of symmetry-protected order in spin-1 systems and their use in quantum applications.
As confirmed by the extreme tsunami events over the last decade (the 2004 Indian Ocean, 2010 Chile and 2011 Japan tsunami events), mitigation measures and effective evacuation planning are needed to reduce disaster risks. Modeling tsunami evacuations is an alternative means to analyze evacuation plans and possible scenarios of evacuees’ behaviors. In this paper, practical applications of an agent-based tsunami evacuation model are presented to demonstrate the contributions that agent-based modeling has added to tsunami evacuation simulations and tsunami mitigation efforts. A brief review of previous agent-based evacuation models in the literature is given to highlight recent progress in agent-based methods. Finally, challenges are noted for bridging gaps between geoscience and social science within the agent-based approach for modeling tsunami evacuations.
This article critically scrutinizes the perceived view that the emergence of non-core dative constructions in Modern Hebrew is due to a Slavic-Yiddish influence. It studies the Biblical and Mishnaic sources, showing that these language strata contain highly similar constructions to the ones in Modern Hebrew. It additionally shows that parallel constructions existed in languages spoken in the Jewish communities at the time of the revival, revealing that this linguistic phenomenon is typologically widely attested. We therefore claim that this could be an example of an internalization of the old grammar in the new spoken language, enhanced by the fact that similar constructions are reflected in the non-Hebrew native languages of the revival era speakers. These speakers, at the same time, imported into their colloquial Hebrew a sub-type of non-core dative—the discursive dative—to which they could not have been exposed through the ancient written texts, since this type of dative construction occurs only in the spoken language.
Elizabeth Fernandez, Zeira, Anat , Vecchiato, Tiziano , ו Canali, Cinzia . 2015. “Reducing Poverty And Investing In Children And Families”. Theoretical And Empirical Insights Into Child And Family Poverty: Cross National Perspectives, Pp. 303–311.
Anupama Mittal, Chitkara, Deepak , Kumar, Neeraj , Pawar, Rajendra , Domb, Avi , ו Corn, Ben . 2015. “Regional Drug Therapy: Polymeric Carriers For”. בתוך Encyclopedia Of Biomedical Polymers And Polymeric Biomaterials, 11 Volume Set, Pp. 6951–6972. CRC Press.
