Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

Background: Parkinson’s disease is a neurodegenerative disease in which the progressive loss of dopaminergic neurons leads to initially sporadic and eventually widespread damage of the nervous system resulting in significant musculoskeletal and cognitive deterioration. Loss of motor function alongside increasing cognitive impairment is part of the natural disease progression. Gait is often considered an automatic activity; however, walking is the result of a delicate balance of multiple systems which maintain the body’s center of mass over an ever-changing base of support. (...) It is a complex motor behavior that requires components of attention and memory to prevent falls and injury. In addition, evidence points to the critical role of salient visual information to gait adaptability. There is a growing understanding that treatment for PD needs to address movement as it occurs naturally and walking needs to be practiced in more complex environments than traditional therapy has provided.MethodsIn this single-blinded randomized-controlled pilot study, an immersive treadmill training was piloted to determine feasibility and preliminary efficacy on gait and cognition in people with PD. Eighteen participants with Hoehn and Yahr stages I-III PD were randomized to either an intervention or a waitlist control group. Following baseline data collection, the intervention group trained for 30 min, three times/week for 4 weeks on a split belt treadmill combined with a first-person immersive video game targeting visuospatial skills and working memory. Assessment was repeated after 4 weeks of training for the experimental group and 1-month after baseline for the control group. Primary motor outcomes were captured with the APDM Opal sensors during 6 MWT, TUG, and TUG Cognitive. Secondary outcomes of cognition were measured with the Montreal Cognitive Assessment, Verbal Fluency and the Symbol Digit Modality Test. Within subject differences were calculated using the Wilcoxon Signed Ranked Test and between subject comparisons were analyzed using the Mann Whitney U-test.ResultsThis novel treadmill training program was well-tolerated with all participants in the intervention group completing 4 weeks of training three times a week without any adverse effects. After immersive cognitive motor training, the experimental group made clinically relevant improvements in gait speed and walking distance during the 6 MWT while members of the control group showed no change or decreased gait speed and walking distance over the 1-month trial. In addition, the experimental group demonstrated significant improvement for the TUG Cognitive and those changes were greater than the control group. The experimental group also improved scores on MoCA and SDMT cognitive outcome measures while the control group did not.ConclusionThe use of immersive gaming technology to engage specific areas of cognition related to gait is feasible in PD. The treadmill training program paired with a customized interactive video game improved walking velocity in addition to non-significant but consistent improvements in other gait measures and cognitive performance in participants with early to mid-stage PD. (shrink)

To attain native-like competence, second language (L2) learners must establish mappings between familiar speech sounds and new phoneme categories. For example, Spanish learners of English must learn that [d] and [ð], which are allophones of the same phoneme in Spanish, can distinguish meaning in English (i.e. /deɪ/ ‘day’ and /ðeɪ/ ‘they’). Because adult listeners are less sensitive to allophonic than phonemic contrasts in their native language (L1), novel target language contrasts between L1 allophones may pose special difficulty for L2 learners. (...) We investigate whether advanced Spanish late-learners of English overcome native language mappings to establish new phonological relations between familiar phones. We report behavioral and magnetoencepholographic (MEG) evidence from two experiments that measured the sensitivity and pre-attentive processing of three listener groups (L1 English, L1 Spanish, and advanced Spanish late-learners of English) to differences between three nonword stimulus pairs ([idi]-[iði], [idi]-[iɾi], and [iði]-[iɾi]) which differ in phones that play a different functional role in Spanish and English. Spanish and English listeners demonstrated greater sensitivity (larger d’ scores) for nonword pairs distinguished by phonemic than by allophonic contrasts, mirroring previous findings. Spanish late-learners demonstrated sensitivity (large d’ scores and MMN responses) to all three contrasts, suggesting that these L2 learners may have established a novel [d]-[ð] contrast despite the phonological relatedness of these sounds in the L1. Our results suggest that phonological relatedness influences perceived similarity, as evidenced by the results of the native speaker groups, but may not cause persistent difficulty for advanced L2 learners. Instead, L2 learners are able to use cues that are present in their input to establish new mappings between familiar phones. (shrink)

Studying the neural correlates of conscious awareness depends on a reliable comparison between activations associated with awareness and unawareness. One particularly difficult confound to remove is task performance capacity, i.e. the difference in performance between the conditions of interest. While ideally task performance capacity should be matched across different conditions, this is difficult to achieve experimentally. However, differences in performance could theoretically be corrected for mathematically. One such proposal is found in a recent paper by Lamy, Salti and Bar-Haim [Lamy (...) D, Salti M, Bar-Haim Y. Neural correlates of subjective awareness and unconscious processing: an ERP study. J Cognitive Neurosci 2009,21:1435-46], who put forward a corrective method for an electroencephalography experiment. We argue that their analysis is essentially grounded in a version of High Threshold Theory, which has been shown to be inferior in general to Signal Detection Theory. We show through a series of computer simulations that their correction method only partially removes the influence of perfor- mance capacity, which can yield misleading results. We present a mathematical correction method based on Signal Detection Theory that is theoretically capable of removing performance capacity confounds. We discuss the limitations of mathemati- cally correcting for performance capacity confounds in imaging studies and its impact for theories about consciousness. (shrink)

Western democracy is now at a critical juncture. Some worry that power has been wrested from the people and placed in the hands of a small political elite. Others argue that the democratic system gives too much power to a populace that is largely ill-informed and easily swayed by demagogues. This classic study of democratic principles is thus now more relevant than ever. A renowned historian of antiquity and political philosophy, Sir M.I. Finley offers a comparative analysis of Greek and (...) modern conceptions of democracy. As he puts the ancient Greeks in dialogue with their contemporary counterparts, Finley tackles some of the most pressing issues of our day, including public apathy, partisanship, consensus politics, distrust of professional politicians, and the limits of free speech. Including three lectures that Finley delivered at Rutgers University, plus two additional essays that further illuminate his thinking, _Democracy Ancient and Modern _explores the dramatic differences between the close-knit civil society of the ancient Greeks and our own atomized mass societies. By mapping out democracy’s past and its present manifestations, this book helps us plot a course for democracy’s future. (shrink)

Both society and plasma (ionized gas) fluid are composed of active, interactive, and free, individuals. These individuals are responded to any internal and external effects (fields for plasma), and exhibit collective behaviour. According to this structure, there are a wide range of similarities between the plasma fluid and the society. The nature of fluidity of plasma arises from the interaction of its free interactive charges, so the society may behave as a fluid owing to the free interactive individuals. This fluid (...) model may explain many social phenomena like social instability, diffusion, flow, viscosity...So the society behaves as a sort of intellectual fluid. (shrink)

In his consideration of thought development August Comte has been proposed a three stage model of thinking development. The way that led to any new type of think may repeat itself to produce another new type. So the way that led to philosophy of science may be repeated. It perhaps to attribute the mechanism of thought evolution to a process of accumulation of unanswered questions which is flowed by a declination in that type of thinking interest. One can say that (...) the accumulation of unverified huge new physics theories and ideas; leads to a declination in physics interest and that may lead to a new type of philosophy. The proposed new type is the philosophy of technology, and probably can be considered as the fourth stage according to Comte model. (shrink)

Background The post-trial period is the time period after the end of study drug administration. It is unclear whether post-trial arrangements for patient surveillance are routinely included in study protocols and consents, and whether research ethics boards (REB) consider the post-trial period. Objectives The objective was to determine whether trial protocols and consent forms reviewed by the REB describe procedures for post-trial period surveillance. Methods An observational study of protocols of randomised trials of chronic therapies for cardiac conditions, approved by (...) the REB of two academic institutions affiliated with the University of Toronto in Canada (University Health Network and Mount Sinai Hospital) from 1995 to 2007. Plans for patient surveillance in the post-trial period described in the protocol or in the consent form before and after REB approval were recorded. Results 42 studies were identified including 18 heart failure and 15 coronary artery disease trials. Only four studies planned a clinical visit after trial termination, and an additional three planned a telephone contact after trial completion. Five trials submitted consent forms to the REB with a discussion of the post-trial period. Conclusions The majority of protocols and consent forms did not discuss plans for post-trial period surveillance. The post-trial period and the REB approval process could be improved by systematic follow-up being described in the protocol and consent form. The small number of trial protocols evaluated in the study may impair the degree to which the results can be generalised. (shrink)

The article presents the conceptualization of philosophical education, in the context of which the evolution of the development of society from informational to smart society takes place. The purpose of the article is to reveal the conceptualization of philosophical education in the context of the idea of a smart society and to show that philosophical education does not stand still but develops along with the development of science and technology, which requires the development of a conceptual and categorical apparatus. Research (...) objectives: to show the development of philosophical knowledge, in the context of which new innovative ideas are ripening; to reveal that the concept of a smart society is based on the expectation or belief in the ability of modern smart technologies to positively influence social processes and lead to a new qualitative state of all social life, which is called a smart society; to prove that much in solving all these problems depends on the state of education, including philosophical and ideological, not only developing our cognitive abilities, but also forming a responsible and demanding attitude to goal setting, the choice of basic life values. Analysis of recent research and publications, which presents a solution to this problem. We rely on the works of I.Ardashkin, V.Voronkova, M.Kastels, O.Kivlyuk, K.Korsak, A.Lazarevich, R.Oleksenko, O.Punchenko, which in one way or another reflected the problem of the formation of a smart society. The research methodology is the dialectical, historical, systemic, informational methods, which allowed to penetrate deeply into the evolution of philosophical knowledge that is not in mass, but develops with the development of science, technique and technology. The result of research - based smart society the development of information and computer technologies that lead to breakthrough technologies and innovative development It is noted that the proposed reorganization of the system of social-humanitarian education in the universities of the Republic of Belarus intended to raise to the level of philosophical training of domestic specialists. (shrink)

The purpose of this article is to define the limits of technocentrism through the analysis of the limiting opportunities of technique and technology from certain value positions. Theoretical basis. The philosophical anthropology of Helmut Plessner was the research methodology. Originality. The institutional use of technology gives it the character of a social phenomenon and turns it into technology. The ability of individuals, which is aimed at achieving a certain goal with the help of certain sustainable techniques, is not yet technology (...) in itself but is only a certain author’s technique. Such subjectively acquired technique can be turned into socially used technology, otherwise, it will be lost. Technology is a technique that has gained recognition and has been mastered by those who did not invent it but used the algorithm proposed by the inventor, a detailed and functionally sound explanation, a method of constructing this technique. But the main thing is that technology is a technique that has received an acceptable justification for society. Conclusions. Technology is not only a means of achieving the goal, it is a way for a human being to transform the world. As such, technology is a component of human himself/herself and changes human – more precisely, a human being changed himself/herself with the help of technologies that he/she creates. However, this creates certain limits of such transformations: technology cannot replace humans in their ability to self-reproduce. Technology is always an element of social communication: the success of communication is interdependent on the success of the technology. Social modernization includes new technologies, but a more important component of social modernization is the new values for which these new technologies are created. Human evolution generates the technocratism at a certain stage. But to the extent that technocracy begins to contradict the values of humans and society, it loses its source of development – human creativity. (shrink)

Познавательная культура - системная совокупность исторически специфических средств и приемов, методов и форм, традиций и новаций, идеалов и критериев, норм и предрассудков и т.п. элементов интеллектуального творчества индивидуального или коллективного субъекта, приобщения его к результатам познания, социальным и культурным ценностям. Содержательные составляющие познавательной культуры характеризуют как уровень и степень развития теоретической, научной деятельности, так и ненаучного, вненаучного, повседневного и обыденного познания, фиксируя определенный этап развития духовных творческих способностей личности или социума, обеспечивающих и обслуживающих их познавательное отношение к действительности. Речь идет (...) об особенностях деятельности людей по производству, хранению, трансляции и материализации знаний. (shrink)

Current issues concerning the nature of ancestry and homology are discussed with reference to the evolutionary origin of the tetrapod limb. Homologies are argued to be complex conjectural inferences dependant upon a pre-existing phylogenetic analysisand a theoretical model of the evolutionary development of ontogenetic information. Ancestral conditions are inferred primarily from character (synapomorphy/homology) distributions within phylogeny, because of the deficiencies of palaeontological data. Recent analyses of tetrapod limb ontogeny, and the diverse, earliest morphologies known from the fossil record, are inconsistent (...) with typological concepts such as fixed ancestral patterns or bauplans, emphasising the incompatibility of these with evolutionary continuity. The evolutionary origin of the tetrapod limb is also examined in the light of its recent discussion in developmental genetics. While this field promises to reveal more of the fundamental ontogenetic content of homology (identity), at present it is concerned mostly with the abstraction of a new set of types, rather than investigating diversity and change. (shrink)