Neurotrophins (NTs) are {?AUTHOR} a family of structurally related, secreted proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons.1,2 Among these, BDNF (brain‐derived neurotrophic factor) has drawn considerable interest because both its synthesis and secretion are increased by physiological levels of activity, indicating a unique role of this neurotrophin in coupling neuronal activity to structural and functional properties of neuronal circuits. In addition to its classical neurotrophic effects, which are evident within (...) hours or days and which usually result from changes in cellular gene expression, BDNF exerts acute effects on synaptic transmission and is involved in the induction of long‐term potentiation. Many of these rapid effects of BDNF are mediated by its modulation of ion channel properties following TrkB‐mediated activation of intracellular second messenger cascades and protein phosphorylation. However, recent reports have shown that BDNF not only acts as a modulator of ion channels, but can also directly and rapidly gate a Na+ channel, thereby assigning BDNF the properties of a classical excitatory transmitter. Thus, BDNF, in addition its role as a potent neuromodulator, emerges as an excitatory transmitter‐like substance which acutely controls resting membrane potential, neuronal excitability, synaptic transmission and participates in the induction of synaptic plasticity. BioEssays 26:1185–1194, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

I examine the issue of persistence over time in thecontext of the special theory of relativity (SR). Thefour-dimensional ontology of perduring objects isclearly favored by SR. But it is a different questionif and to what extent this ontology is required, andthe rival endurantist ontology ruled out, by thistheory. In addressing this question, I take theessential idea of endurantism, that objects are whollypresent at single moments of time, and argue that itcommits one to unacceptable conclusions regardingcoexistence, in the context of SR. (...) I then propose anddiscuss a plausible account of coexistence forperduring objects, which is free of these defects. This leaves the endurantist room for some maneuvers. I consider them and show that they do not really helpthe endurantist out. She can accommodate the notionof coexistence in the relativistic framework only atthe cost of renouncing central endurantist intuitions. (shrink)

«Los vuelos al espacio cósmico no se pueden detener. Esta no es una tarea de un sólo hombre cualquiera ni siquiera de un grupo de gente. Es un proceso histórico al que la humanidad llegó en su desarrollo normalmente». Yuri Gagarin (Primer cosmonauta del planeta Tierra)En el artículo se examinan las cuestiones relacionadas con el vuelo del hombre al espacio cósmico. Al principio se enumeran mitos y obras de ficción de los siglos pasados en los que se exponían diferentes ideas (...) y métodos de vuelo del hombre al espacio, entre éstos, los que proponían los científicos españoles. Más adelante, se mencionan los principales logros de la técnica espacial de cohetes de Rusia y, en primer lugar, del primer vuelo espacial del mundo de Yuri Alekséyevich Gagarin el 12 de abril de 1961. Se pone especial atención en la resolución de uno de los problemas más importantes: la creación del cohete portador que garantizó la puesta en órbita terrestre de la nave espacial de Gagarin «Vostok». En el artículo, la atención principal se presta a la estación «Mir». Se describe brevemente la prehistoria de su creación, se exponen los resultados de las investigaciones realizadas y se presentan los informes globales de los resultados de su vuelo de 15 años de duración. (shrink)

This ambitious book looks into the reasons for the exceptional durability of the Chinese empire, which lasted for more than two millennia (221 B.C.E. - 1911 C.E.). Yuri Pines identifies the roots of the empire's longevity in the activities of thinkers of the Warring States period (453-221 B.C.E.), who, in their search for solutions to an ongoing political crisis, developed ideals, values, and perceptions that would become essential for the future imperial polity. In marked distinction to similar empires worldwide, the (...) Chinese empire was envisioned and to a certain extent 'preplanned' long before it came into being. As a result, it was not only a military and administrative construct, but also an intellectual one. Pines makes the argument that it was precisely its ideological appeal that allowed the survival and regeneration of the empire after repeated periods of turmoil. "Envisioning Eternal Empire" presents a panoptic survey of philosophical and social conflicts in Warring States political culture. By examining the extant corpus of preimperial literature, including transmitted texts and manuscripts uncovered at archaeological sites, Pines locates the common ideas of competing thinkers that underlie their ideological controversies. This bold approach allows him to transcend the once fashionable perspective of competing 'schools of thought' and show that beneath the immense pluralism of Warring States thought one may identify common ideological choices that eventually shaped traditional Chinese political culture. The result is a refreshingly novel look at the foundational period in Chinese intellectual history. (shrink)

We illustrate the glorious history of logical foundations and discuss the uncertain future.

In this paper I develop three different arguments against the thesis that knowledge-how is a kind of knowledge-that. Knowledge-that is widely thought to be subject to an anti-luck condition, a justified or warranted belief condition, and a belief condition, respectively. The arguments I give suggest that if either of these standard assumptions is correct then knowledge-how is not a kind of knowledge-that. In closing I identify a possible alternative to the standard Rylean and intellectualist accounts of knowledge-how. This alternative view (...) illustrates that even if the arguments given here succeed it might still be reasonable to hold that knowing how to do something is a matter of standing in an intentional relation to a proposition other than the knowledge-that relation. (shrink)

Although considerations based on contemporary space-time theories, such as special and general relativity, seem highly relevant to the debate about persistence, their significance has not been duly appreciated. My goal in this paper is twofold: (1) to reformulate the rival positions in the debate (i.e., endurantism [three-dimensionalism] and perdurantism [four-dimensionalism, the doctrine of temporal parts]) in the framework of special relativistic space-time; and (2) to argue that, when so reformulated, perdurantism exhibits explanatory advantages over endurantism. The argument builds on the (...) fact that four-dimensional entities extended in space as well as time are relativistically invariant in a way three-dimensional entities are not. (shrink)

in D. Dieks (ed.), The Ontology of Spacetime, Vol. 2. Elsevier, forthcoming.

Is there a successful regress argument against intellectualism? In this article I defend the negative answer. I begin by defending Stanley and Williamson's (2001) critique of the contemplation regress against Noë (2005). I then identify a new argument – the employment regress – that is designed to succeed where the contemplation regress fails, and which I take to be the most basic and plausible form of a regress argument against intellectualism. However, I argue that the employment regress still fails. Drawing (...) on the previous discussion, I criticise further regress arguments given by Hetherington (2006) and Noë (2005). (shrink)

To state an important fact about the photon, physicists use such expressions as (1) “the photon has zero (null, vanishing) mass” and (2) “the photon is (a) massless (particle)” interchangeably. Both (1) and (2) express the fact that the photon has no non-zero mass. However, statements (1) and (2) disagree about a further fact: (1) attributes to the photon the property of zero-masshood whereas (2) denies that the photon has any mass at all. But is there really a difference between (...) saying that something has zero mass (charge, spin, etc.) and saying that it has no mass (charge, spin, etc.)? Does the distinction cut any physical or philosophical ice? I argue that the answer to these questions is yes. Put briefly, the claim of this paper is that some zero-value physical quantities are not mere “privations”, “absences” or “holes in being”. They are respectable properties in the same sense in which their non-zero partners are. This, I will show, has implications for the debate between two rival views of the nature of property, dispositionalism and categoricalism. (shrink)

The article analyzes the structure and manifestations of everyday life as the sphere of the empirical life of the individual believer and the religious community. Patterns of everyday life are not confined to certain universal conceptual or value systems, as there is no ready-made standards and rules of their formation. Everyday life is intersubjective space of social relations in which religious individuals, communities, institutions self-identified based on form of reproduction of sociality. Religious everyday life determined by ordinary consciousness, practices, social (...) aspects of life in the religious community, which are constituted by communication. The main religious structures of everyday life is mental cut ordinary religious consciousness, religious practice, religious experience, religious communication, religious stereotypes. Everyday life is the sphere of interaction between the social and the transcendental worlds, in which religious practices are an integral social relationships and the objectification of religious experience through the prism of individual membership to a specific religion, a means of inclusion of transcendence in the context of everyday life. Religious practices reflect understanding of a religious individual objects of the supernatural world, which is achieved through social experience, intersubjective interaction, experience of transcendental reality. The everyday life of the believing personality is formed in the dynamics of tradition and innovation, the mechanism of interaction of which affects the space of social existence. It exists within the private and public space and time, differing openness within the life-world. Continuous modification of everyday life, change its fundamental structures is determined by the process of modern social and technical transformation of society. (shrink)

The author analyses some problems discussed in the article of Vadim Mezhuev. He discusses the ways in which historians deal with their own scientific problems in the light of philosophical problems of sciences. According to Yu. Nikiforov, a philosopher can always talk about the future which is yet to come; a historian sees the future through the present of the processes which she describes. The author argues that a reconstruction of the past is always based on the knowledge of the (...) present. (shrink)

The author discusses A. M. Dorozhkin’s ideas about constructing and typology of “trading zones”. He considers the influence of the substantive economics’ on science and education. The author argues that the universality of the institutions of reciprocity, redistribution and trade makes possible their stability in the process of institutionalization of scientific and educational activities.

In this paper, the ethical, legal, and social implications of Thailand’s surrogacy regulations from both domestic and global perspectives are explored. Surrogacy tourism in Thailand has expanded since India strengthened its visa regulations in 2012. In 2015, in the wake of a major scandal surrounding the abandonment of a surrogate child by its foreign intended parents, a law prohibiting the practice of surrogacy for commercial purposes was enacted. Consequently, a complete ban on surrogacy tourism was imposed. However, some Thai physicians (...) and surrogate mothers cross into neighboring countries to provide foreign clients with the commercial surrogacy services that are forbidden in Thailand. Under this legislation, the needs of Thai couples who are unable to conceive are accommodated by legally accessible, non-commercial surrogacy services; however, there is currently no provision in place aimed at protecting the rights and interests of surrogate mothers and children. It is widely believed that the abolition of surrogacy tourism, an industry that give rise to several major scandals, and legal access to surrogacy by Thai couples were the Thai government’s primary goal in implementing this legislation. (shrink)

This paper is a reaction to the following remark by grzegorczyk: "the compound sentences are not a product of experiment. they arise from reasoning. this concerns also negations; we see that the lemon is yellow, we do not see that it is not blue." generally, in science the truth is ascertained as indirectly as falsehood. an example: a litmus-paper is used to verify the sentence "the solution is acid." this approach gives rise to a (very intuitionistic indeed) conservative extension of (...) the heyting logic satisfying natural duality laws. (shrink)

Yuri Balashov sets out major rival views of persistence--endurance, perdurance, and exdurance--in a spacetime framework and proceeds to investigate the implications of Einstein's theory of relativity for the debate about persistence. His overall conclusion--that relativistic considerations favour four-dimensionalism over three-dimensionalism--is hardly surprising. It is, however, anything but trivial. Contrary to a common misconception, there is no straightforward argument from relativity to four-dimensionalism. The issues involved are complex, and the debate is closely entangled with a number of other philosophical disputes, including (...) those about the nature and ontology of time, parts and wholes, material constitution, causation and properties, and vagueness. (shrink)

I offer an argument in defense of four-dimensionalism, the view that objects are temporally, as well as spatially extended. The argument is of the inference-to-the-best-explanation variety and is based on relativistic considerations. It deals with the situation in which one and the same object has different three-dimensional shapes at the same time and proceeds by asking what sort of thing it must be in order to present itself in such different ways in various "perspectives" (associated with moving reference frames) without (...) being different from itself. I argue that the best answer is that the object must be four-dimensional. It will then have differing 3D shapes in different perspectives because such shapes are intrinsic properties of its 3D parts. (shrink)

A common belief is that evolution generally proceeds towards greater complexity at both the organismal and the genomic level, numerous examples of reductive evolution of parasites and symbionts notwithstanding. However, recent evolutionary reconstructions challenge this notion. Two notable examples are the reconstruction of the complex archaeal ancestor and the intron‐rich ancestor of eukaryotes. In both cases, evolution in most of the lineages was apparently dominated by extensive loss of genes and introns, respectively. These and many other cases of reductive evolution (...) are consistent with a general model composed of two distinct evolutionary phases: the short, explosive, innovation phase that leads to an abrupt increase in genome complexity, followed by a much longer reductive phase, which encompasses either a neutral ratchet of genetic material loss or adaptive genome streamlining. Quantitatively, the evolution of genomes appears to be dominated by reduction and simplification, punctuated by episodes of complexification. (shrink)

Background In an increasingly globalized world, legal protocols related to health care that are both effective and culturally sensitive are paramount in providing excellent quality of care as well as protection for physicians tasked with decision making. Here, we analyze the current medicolegal status of brain death diagnosis with regard to end-of-life care in Japan, China, and South Korea from the perspectives of front-line health care workers. Main body Japan has legally wrestled with the concept of brain death for decades. (...) An inability to declare brain death without consent from family coupled with cultural expectations of family involvement in medical care is mirrored in other Confucian-based cultures and may complicate care for patients from these countries when traveling or working overseas. Within Japan, China, and South Korea, medicolegal shortcomings in the diagnosis of brain death act as a great source of stress for physicians and expose them to potential public and legal scorn. Here, we detail the medicolegal status of brain death diagnosis within Japan and compare it to China and South Korea to find common ground and elucidate the impact of legal ambiguity on health care workers. Conclusion The Confucian cultural foundation of multiple Asian countries raises common issues of family involvement with diagnosis and cultural considerations that must be met. Leveraging public education systems may increase awareness of brain death issues and lead to evolving laws that clarify such end-of-life issues while protecting physicians from sociocultural backlash. (shrink)

This article examines the method of reflective equilibrium (RE) and its role in philosophical inquiry. It begins with an overview of RE before discussing some of the subtleties involved in its interpretation, including challenges to the standard assumption that RE is a form of coherentism. It then evaluates some of the main objections to RE, in particular, the criticism that this method generates unreasonable beliefs. It concludes by considering how RE relates to recent debates about the role of intuitions in (...) philosophy. (shrink)

Automated classification of legal documents has been the subject of extensive research in recent years. However, this is still a challenging task for long documents, since it is difficult for a model to identify the most relevant information for classification. In this paper, we propose a two-stage supervised learning approach for the classification of petitions, a type of legal document that requests a court order. The proposed approach is based on a word-level encoder–decoder Seq2Seq deep neural network, such as a (...) Bidirectional Long Short-Term Memory (BiLSTM) or a Bidirectional Encoder Representations from Transformers (BERT) model, and a document-level Support Vector Machine classifier. To address the challenges posed by the lengthy legal documents, the approach introduces a human-in-the-loop approach, whose task is to localize and tag relevant segments of text in the word-level training part, which dramatically reduces the dimension of the document classifier input vector. We performed experiments to validate our approach using a real-world dataset comprised of 270 intermediate petitions, which were carefully annotated by specialists from the 15th civil unit of the State of Alagoas, Brazil. Our results revealed that both BiLSTM and BERT-Convolutional Neural Networks variants achieved an accuracy of up to 95.49%, and also outperformed baseline classifiers based on the Term Frequency–Inverse Document Frequency test vectorizer. The proposed approach is currently being utilized to automate the aforementioned justice unit, thereby increasing its efficiency in handling repetitive tasks. (shrink)

How should intellectualists respond to apparent Gettier-style counterexamples? Stanley offers an orthodox response which rejects the claim that the subjects in such scenarios possess knowledge-how. I argue that intellectualists should embrace a revisionary response according to which knowledge-how is a distinctively practical species of knowledge-that that is compatible with Gettier-style luck.

It is often said that ‘what it is like’-knowledge cannot be acquired by consulting testimony or reading books [Lewis 1998; Paul 2014; 2015a]. However, people also routinely consult books like What It Is Like to Go to War [Marlantes 2014], and countless ‘what it is like’ articles and youtube videos, in the apparent hope of gaining knowledge about what it is like to have experiences they have not had themselves. This article examines this puzzle and tries to solve it by (...) appealing to recent work on knowing-wh ascriptions. In closing I indicate the wider significance of these ideas by showing how they can help us to evaluate prominent arguments by Paul [2014; 2015a] concerning transformative experiences. (shrink)

Surrogacy tourism in Asian countries has surged in recent decades due to affordable prices and favourable regulations. Although it has recently been banned in many countries, it is still carried out illegally across borders. With demand for surrogacy in developed countries increasing and economically vulnerable Asian women lured by lucrative compensation, there are efforts by guest countries to ease the strict surrogacy regulations in host countries. Despite a shift toward “altruistic surrogacy”, commercial surrogacy persists. Recent research carried out by international (...) organizations that seek to establish a legal relationship between the commissioning parents and children in cross-border surrogacy arrangements, under the guise of the “best interests of the child,” appears to promote a resurgence of overseas commercial surrogacy rather than restrict it. Further commercialization of surrogacy should be prevented by carefully investigating the reality of the surrogacy process. (shrink)

Malignant cells are characterized by an increased content of endogenous formaldehyde formed as a by‐product of biosynthetic processes. Accumulation of formaldehyde in cancer cells is combined with activation of the processes of cellular formaldehyde clearance. These mechanisms include increased ALDH and suppressed ADH5/FDH activity, which oncologists consider poor and favorable prognostic markers, respectively. Here, the sources and regulation of formaldehyde metabolism in cancer cells are reviewed. The authors also analyze the participation of oncoproteins such as fibulins, FGFR1, HER2/neu, FBI‐1, and (...) MUC1‐C in the control of genes related to formaldehyde metabolism, suggesting the existence of two mutually exclusive processes in cancer cells: 1) production and 2) oxidation and elimination of formaldehyde from the cell. The authors hypothesize that the study of the anticancer properties of disulfiram and alpha lipoic acid – which affect the balance of formaldehyde in the body – may serve as the basis of future anticancer therapy. (shrink)

A growing literature in economics studies ethical behavior and honesty, as it is imperative for functioning societies in a world of incomplete information and contracts. A majority of studies found more pronounced dishonesty among teams compared to individuals. Scholars identified certain nudges as effective and cost-neutral measures to curb individuals' dishonesty, yet little is known about the effectiveness of such nudges for teams. We replicate a seminal nudge treatment effect, signing on the top of a reporting form vs. no signature, (...) with individuals and confirm the original nudge treatment effect. We further ran the same experiment with teams of two that have to make a joint reporting decision. Our results show the effectiveness of the nudge for teams, which provides further confidence in the applicability of the nudge. (shrink)

Previous work suggests that Asians allocate more attention to configuration information than Caucasian Americans do. Yet this cultural variation has been found only with stimuli such as natural scenes and objects that require both feature- and configuration-based processing. Here, we show that the cultural variation also exists in face perception—a domain that is typically viewed as configural in nature. When asked to identify a prototypic face for a set of disparate exemplars, Japanese were more likely than Caucasian Americans to use (...) overall resemblance rather than feature matching. Moreover, in a speeded identity-matching task, Japanese were more accurate than Americans in identifying the spatial configuration of features (e.g., eyes). Together, these findings underscore the robustness of culture’s influences on cognition. (shrink)

Most four-dimensionalists, including both worm and stage theorists, endorse mereological universalism, the thesis that any class of objects has a fusion. But the marriage of fourdimensionalism and universalism is unfortunate and unprofitable: it creates a recalcitrant problem for stage theory’s account of lingering properties, such as writing ‘War and Piece’ and traveling across the tennis court, which take time to be instantiated. This makes it necessary to impose a natural restriction on diachronic composition.

Many philosophers accept a view – what I will call the intuition picture – according to which intuitions are crucial evidence in philosophy. Recently, Williamson has argued that such views are best abandoned because they lead to a psychologistic conception of philosophical evidence that encourages scepticism about the armchair judgements relied upon in philosophy. In this paper I respond to this criticism by showing how the intuition picture can be formulated in such a way that: it is consistent with a (...) wide range of views about not only philosophical evidence but also the nature of evidence in general, including Williamson's famous view that E = K; it can maintain the central claims about the nature and role of intuitions in philosophy made by proponents of the intuition picture; it does not collapse into Williamson's own deflationary view of the nature and role of intuitions in philosophy; and it does not lead to scepticism. (shrink)

The nature of persistence of physical objects over time has been intensely debated in contemporary metaphysics. The two opposite views are widely known as "endurantism" (or "three-dimensionalism") and "perdurantism" ("four-dimensionalism"). According to the former, objects are extended in three spatial dimensions and persist through time by being wholly present at any moment at which they exist. On the rival account, objects are extended both in space and time and persist by having "temporal parts," no part being present at more than (...) one time. Relativistic considerations seem highly relevant to this debate. But they have played little role in it so far. This paper seeks to remedy that situation. I argue that considerations based on the special theory of relativity and the notion of coexistence favor perdurantism over endurantism. (shrink)

This chapter explores the relationship between knowing-how and skill, as well other success-in-action notions like dispositions and abilities. I offer a new view of knowledge-how which combines elements of both intellectualism and Ryleanism. According to this view, knowing how to perform an action is both a kind of knowing-that (in accord with intellectualism) and a complex multi-track dispositional state (in accord with Ryle’s view of knowing-how). I argue that this new view—what I call practical attitude intellectualism—offers an attractive set of (...) solutions to various puzzles concerning the connections between knowing-how and abilities and skills to perform intentional actions. (shrink)

Este ensayo plantea una cuestión filosófica perseguida como investigación histórica que desemboca en una explicación sociológica en torno a la medición de la ciencia. Medir, etimológicamente relacionado con una praecisio adquiere su sentido más profundo en una era postontológica para describir las implicaciones culturales de un mundo privado de metafísica. Basado en un relato sucinto del surgimiento del pensamiento bibliométrico enmarcado por el debate historiográfico de principios del siglo XX entre historiadores seriales e historiadores del evento, este ensayo une tanto (...) el significado postontológico como la evidencia histórica en un análisis sociológico de la ciencia y políticas tecnológicas en la Colombia del cambio de siglo que conlleva una transformaciónradical de la universidad como institución social, del estatus del conocimiento en la sociedad contemporánea y de la identidad de nosotros los académicos que habitamos ese espacio. (shrink)

The theory of trees with additional unary predicates and quantification over nodes and branches embraces a rich branching time logic. This theory was reduced in the companion paper to the first-order theory of binary, bounded, well-founded trees with additional unary predicates. Here we prove the decidability of the latter theory.