Dicer is a key player in microRNA (miRNA) and RNA interference (RNAi) pathways, processing miRNA precursors and doublestranded RNA into ~21-nt-long products ultimately triggering sequence-dependent gene silencing. Although processing of substrates in vertebrate cells occurs in the cytoplasm, there is growing evidence suggesting Dicer is also present and functional in the nucleus. To address this possibility, we searched for a nuclear localization signal (NLS) in human Dicer and identified its C-terminal double-stranded RNA binding domain (dsRBD) as harboring NLS activity. We (...) show that the dsRBD-NLS can mediate nuclear import of a reporter protein via interaction with importins β, 7, and 8. In the context of full-length Dicer, the dsRBD-NLS is masked. However, duplication of the dsRBD localizes the full-length protein to the nucleus. Furthermore, deletion of the N-terminal helicase domain results in partial accumulation of Dicer in the nucleus upon leptomycin B treatment, indicating that CRM1 contributes to nuclear export of Dicer. Finally, we demonstrate that human Dicer has the ability to shuttle between the nucleus and the cytoplasm. We conclude that Dicer is a shuttling protein whose steady-state localization is cytoplasmic. (shrink)

Democracy - hope or illusion? Blooming, failing or declining? Our doubts and hesitation make part of unbending efforts to endorse and explain democracy. Who is right - the custodians of promise or the prophets of decline? The book concentrates on doubts. The author tries to explore «the other side of the moon», emphasizing the role of critical thinking, opposing a main-current optimism. Defending democracy we want to generate hope, but hoping may be a dangerous craft. Protecting our hope we are (...) prone to believe that democracy - even if it is not a full success story - is justified in its nature and out of question. How much do we have to forget to sanction this view? This is, in fact, the main question the book raises. It gives voice to those who never, in their writing on democracy, used a flattering tone. Starting with Greek giants - Plato and Aristotle - up to modern and most recent times, going through a broad field of revealing criticism, leaving us with an unsettling feeling that democracy is rather something to be explained than something to be celebrated. Living in democracy, lamenting its underperformances, we must not overlook a fundamental question - in what part do our disappointments reflect the «art of forgetting», allowing us to cast into oblivion all serious doubts originating in a critical discourse on modernity and democracy? (shrink)

Most discussions of the reproducibility crisis focus on its epistemic aspect: the fact that the scientific community fails to follow some norms of scientific investigation, which leads to high rates of irreproducibility via a high rate of false positive findings. The purpose of this paper is to argue that there is a heretofore underappreciated and understudied dimension to the reproducibility crisis in experimental psychology and neuroscience that may prove to be at least as important as the epistemic dimension. This is (...) the communication dimension. The link between communication and reproducibility is immediate: independent investigators would not be able to recreate an experiment whose design or implementation were inadequately described. I exploit evidence of a replicability and reproducibility crisis in computational science, as well as research into quality of reporting to support the claim that a widespread failure to adhere to reporting standards, especially the norm of descriptive completeness, is an important contributing factor in the current reproducibility crisis in experimental psychology and neuroscience. (shrink)

We argue that Yarkoni's proposed solutions to the generalizability crisis are half-measures because he does not recognize that the crisis arises from investigators' underappreciation of the roles of theory in experimental research. Rather than embracing qualitative analysis, the research community should make an effort to develop better theories and work toward consistently incorporating theoretical results into experimental practice.

For a free filter F on $$\omega $$ ω, endow the space $$N_F=\omega \cup \{p_F\}$$ N F = ω ∪ { p F }, where $$p_F\not \in \omega $$ p F ∉ ω, with the topology in which every element of $$\omega $$ ω is isolated whereas all open neighborhoods of $$p_F$$ p F are of the form $$A\cup \{p_F\}$$ A ∪ { p F } for $$A\in F$$ A ∈ F. Spaces of the form $$N_F$$ N F constitute the (...) class of the simplest non-discrete Tychonoff spaces. The aim of this paper is to study them in the context of the celebrated Josefson–Nissenzweig theorem from Banach space theory. We prove, e.g., that, for a filter F, the space $$N_F$$ N F carries a sequence $$\langle \mu _n:n\in \omega \rangle $$ ⟨ μ n : n ∈ ω ⟩ of normalized finitely supported signed measures such that $$\mu _n(f)\rightarrow 0$$ μ n ( f ) → 0 for every bounded continuous real-valued function f on $$N_F$$ N F if and only if $$F^*\le _K{\mathcal {Z}}$$ F ∗ ≤ K Z, that is, the dual ideal $$F^*$$ F ∗ is Katětov below the asymptotic density ideal $${\mathcal {Z}}$$ Z. Consequently, we get that if $$F^*\le _K{\mathcal {Z}}$$ F ∗ ≤ K Z, then: (1) if X is a Tychonoff space and $$N_F$$ N F is homeomorphic to a subspace of X, then the space $$C_p^*(X)$$ C p ∗ ( X ) of bounded continuous real-valued functions on X contains a complemented copy of the space $$c_0$$ c 0 endowed with the pointwise topology, (2) if K is a compact Hausdorff space and $$N_F$$ N F is homeomorphic to a subspace of K, then the Banach space C(K) of continuous real-valued functions on K is not a Grothendieck space. The latter result generalizes the well-known fact stating that if a compact Hausdorff space K contains a non-trivial convergent sequence, then the space C(K) is not Grothendieck. (shrink)

Inequality of incomes is one of the significant factors forming the social capital. Two views dominate among economists dealing with the influence of inequality of income on economic growth. On the one hand, a too low inequality of income does not motivate people to increase the labour productivity. A low inequality of income might result from an extended social care system and overloading GDP with social transfers. A good example of it may be a situation when the unemployed refuses to (...) accept a job offer and prefers the unemployment benefit rather to a slightly higher salary. Moreover, a lack of incentives for the employee who fails to acknowledge the economic sense of increasing the productivity of his work might lead to the slower growth of economy. On the other hand, a contrary view suggests that an increase of the inequality of income has a negative impact on the economy. The accumulation of wealth by a small number of citizens raises doubts about good use of that wealth for investments necessary for the growth of the economy. An excessive inequality of income is confronted with disapproval of the significant part of society and regarded as unfair and unjustified. It may also increase the crime level and decrease the trust and, more generally, lead to the weakening of social capital. The arguments above lead to a hypothesis that the influence of the inequality of income on the growth of the economy has a non-linear character. We confirmed this hypothesis in growth models of the US and Swedish economies. We assess the historically optimal inequality of income measured by the Gini coefficient at 46% and 24% for the US and Sweden respectively. The optimal inequality of income in Poland was assessed previously at 29%. The dissimilarities may result from the cultural differences, educational level differences, ethnic differences and differences in diligence. (shrink)

The paper presents two objections against Putnam’s Twin Earth argument, which was intended to secure semantic externalism. I first claim that Putnam’s reasoning rests on two assumptions and then try to show why these assumptions are contentious. The first objection is that, given what we know about science, it is unlikely that there are any natural-kind terms whose extension is codetermined by a small set of microstructures required by Putnam’s indexical account of extension determination. The second objection is that there (...) may not be a plausible concept of a speech community whose adoption would classify Oscar and Twin Oscar as members of different speech communities and, at the same time, render Oscar and Twin Oscar as being in the same psychological state. I contend that Putnam’s argument fails because both objections are justified. (shrink)

To explore how model building adapts to changing environments, we had participants play “rock-paper-scissors” against a computer that played a frequency bias or a player-dependent bias and then switched. Participants demonstrated their use of prior experience in how quickly they recognized and exploited changes in the computer's play strategy; in general, the more similar the strategies, the more efficient the updating. These findings inform our understanding of previously reported updating impairments in right-brain damaged patients.

What is the meaning of the “Europe” and the idea of unity? For when did a “united” Europe exist? Back when German emperors ineffectively tried to enforce their rule on a territory which was none too large anyway? Or when they were entangled in a dispute with the papacy? Or during the crusades against the Catharists? Or maybe during the Reformation or during the French Revolution when new coalitions of opponents arose? During the Napoleonic Wars which in themselves pay testimony (...) to ruptures and conflicts? The 20th century alone brought two wars. The first already signified, as Jan Patocka once declared, the suicide of Europe. Perhaps, then, Europe does not exist at all anymore? Maybe the politicians’ visions are less than credible? There is no doubt that the idea of a united Europe is a project which affirms the great, creative power of the imagination. Modernity has given birth to very strong temptations which glorify the imagination. (shrink)

Demokracja i erozja tradycji Oświecenia -- Mit, polityka, popkultura -- Przyjaźń i mizantropia : czego uczy nas liberalizm?

There are three intentions (aims) of this paper. First, to focus the attention of readers to three not so well known and least frequently quoted by economists of Mises’s books, namely his 1957 Theory and History: An Interpretation of Social and Economic Evolution, and two closely related The Ultimate Foundation of Economic Science: An Essay on Method (1962), and Epistemological Problems of Economics (1933/1960). The second aim is to outline Mises’s legacy, presented in the form of eleven dimensions of Mises’s (...) Intellectual Universe. The eleven dimensions of Mises’s system are: Economics as science, praxeology, and human action; Methodological dualism; Judgments of value and subjectivism; Individualism; Rationalism and human action; Consumer; Cooperation and competition; Thymology; Mathematics in economics; Predictions; and Historical analysis. Third, to present the main issues related to Mises’s concept of rationalism. There is no mention of Ludwig von Mises’s concept of rationality in a great number of books and papers dealing with the understanding of the rationality of human beings. The concept of rationality proposed by Ludwig von Mises is neglected by modern researchers and economists of different schools, but especially by mainstream economists. A good example of neglecting Mises’s ideas on rationality is the latest book by Nassim Taleb, Skin in the Game: Hidden Asymmetries in Daily Life. Although Taleb’s proposition of understanding rationality and irrationality is very close to the concept of Mises, he does not refer to Mises’s work at all. No single word on Mises in that book! (shrink)

The essay presents some gnoseological themes with reference to the intellect of the separated soul according to John Duns Scotus. Four questions of the Ordinatio IV, d. 45 deal with these themes. In this concret cognitive situation is possible, according to Doctor Subtilis, to get to know the new quiddities of things, in spite of a lack of the empiric cognition. It means leaving behind the conception of generic empiricism and moving to the recognition of more cognitive abilities, as in (...) Aristoteles’s conception. In a post death state intellect continues to have the memory of the quiddities of things known while still connected with the body and can remember concret things and events known by the senses during earthly life. Such a gnoseological notion evidences the cognitive continuity of the human intellect after death, its incorruptibility and cognitive ability at least as such as one had during earthly life. We can see here the connection of philosophic and theological questions, which mutually condition and penetrate each other. According to Scotus it is possible for the intellect of the separated soul to remember the past and to acquire new cognition. Moreover, it is also possible for such an intellect to know the prayers we refer to the blessed in heaven. Such an intellectual approach evidences a strong Augustinian influence on John Duns Scotus’ epistemic conception. (shrink)