Non-player characters (NPCs) are a common feature in contemporary videogames, particularly role-playing games (RPGs). Evidence suggests player relationships with these fictional, digital characters can manifest as deeply emotional experiences that can ‘bleed’ off the screen and affect the daily lives of players. However, research in this area is still in its infancy, and as yet has not been given a thorough conceptual treatment. Applying the sociological phenomenology of Alfred Schütz, this paper will examine the structure of the experiences that players (...) have with NPCs, and how these experiences manifest as meaningful social experiences. By a reconceptualization of the player-NPC relationship as a deeply mediated human-human relationship, this paper aims to build a foundation for further phenomenological study into how players engage with fictional characters in immersive videogame worlds. (shrink)

D‐amino acids are being recognized as functionally important molecules in mammals. We recently identified endogenous D‐cysteine in mammalian brain. D‐cysteine is present in neonatal brain in substantial amounts (mM) and decreases with postnatal development. D‐cysteine binds to MARCKS and a host of proteins implicated in cell division and neurodevelopmental disorders. D‐cysteine decreases phosphorylation of MARCKS in neural progenitor cells (NPCs) affecting its translocation. D‐cysteine controls NPC proliferation by inhibiting AKT signaling. Exogenous D‐cysteine inhibits AKT phosphorylation at Thr 308 and Ser (...) 473 in NPCs. D‐cysteine treatment of NPCs led to 50% reduction in phosphorylation of Foxo1 at Ser 256 and Foxo3a at Ser 253. We hypothesize that in the developing brain endogenous D‐cysteine is as a physiologic regulator of NPC proliferation by inhibiting AKT signaling mediated by Foxo1 and Foxo3a. Endogenous D‐cysteine may regulate mammalian neurodevelopment with roles in schizophrenia and Alzheimer's disease (AD). (shrink)

The nuclear pore complex (NPC) is emerging as a center for recruitment of a class of “difficult to repair” lesions such as double‐strand breaks without a repair template and eroded telomeres in telomerase‐deficient cells. In addition to such pathological situations, a recent study by Su and colleagues shows that also physiological threats to genome integrity such as DNA secondary structure‐forming triplet repeat sequences relocalize to the NPC during DNA replication. Mutants that fail to reposition the triplet repeat locus to the (...) NPC cause repeat instability. Here, we review the types of DNA lesions that relocalize to the NPC, the putative mechanisms of relocalization, and the types of recombinational repair that are stimulated by the NPC, and present a model for NPC‐facilitated repair. (shrink)

We present a game mechanic called pseudo-visibility for games inhabited by non-player characters (NPCs) driven by reinforcement learning (RL). NPCs are incentivized to pretend they cannot see pseudo-visible players: the training environment simulates an NPC to determine how the NPC would act if the pseudo-visible player were invisible, and penalizes the NPC for acting differently. NPCs are thereby trained to selectively ignore pseudo-visible players, except when they judge that the reaction penalty is an acceptable tradeoff (e.g., a guard might accept (...) the penalty in order to protect a treasure because losing the treasure would hurt even more). We describe an RL agent transformation which allows RL agents that would not otherwise do so to perform some limited self-reflection to learn the training environments in question. (shrink)

The cilium/flagellum is a sensory-motile organelle ancestrally present in eukaryotic cells. For assembly cilia universally rely on intraflagellar transport (IFT), a specialised bidirectional transport process mediated by the ancestral and conserved IFT complex. Based on the homology of IFT complex proteins to components of coat protein I (COPI) and clathrin-coated vesicles, we propose that the non- vesicular, membrane-bound IFT evolved as a specialised form of coated vesicle transport from a protocoatomer complex. IFT thus shares common ancestry with all protocoatomer derivatives, (...) including all vesicle coats and the nuclear pore complex (NPC). This has major implications for the evolutionary origin of the cilium. First, it reinforces the tenet that duplication and divergence of pre-existing structures, rather than symbiosis, were the major themes during cilium evolution. Second, it suggests that the initial step in the autogenous origin of the cilium was the establishment of a membrane patch with transmembrane proteins transported by the ancestral vesicle-coating IFT complex. We propose a scenario for how the initial membrane patch gradually protruded to enhance exposure to the environment, then started to move, and finally compartmentalised to render receptor signalling and ciliary beating more efficient. BioEssays 28: 191–198, 2006. © 2006 Wiley periodicals, Inc. (shrink)

A virtual reality translation of Robert Nozick's "Experience Machine" thought experiment from his "Anarchy, State, and Utopia" (1974). These modules are free to download and use in the classroom and for research/x-phi purposes. NPCs are randomized for gender during startup of each run. *Requires an Oculus Rift or HTC Vive and VR capable computer. To open the files, uncompress the downloaded .zip folder and run the executable (.exe) file. -/- V1.2 Fixed missing projector video footage during experience machine sales pitch.

From a formal point of view, the nihilistic propositional calculi, called in this text „npc”, are such propositional calculi that include three unary propositional conectives: T, F, ~, and one binary propositional connective ≡. They read respectively: true, false, untrue that, if and only if. Their theorems are, mong other things, such expressions as: Tp ≡ p, Fp ≡ ~p, with p being a propositional variable. The four npc are presented in this work, i.e. on two-valued, two three-valued, and one (...) four-valued. Moreover, two of them are also paraconsistent calculi. Npc are constructed by means of the axiomatic method. Following the presentation of npc axioms, the four so called n-algebras are introduced. The npc axioms are proved to be adequate to appropriate n-algebras, i.e. sets of theorems and tautologies of each npc are identical. (shrink)

In the paper Busaniche and Cignoli we presented a quasivariety of commutative residuated lattices, called NPc-lattices, that serves as an algebraic semantics for paraconsistent Nelson’s logic. In the present paper we show that NPc-lattices form a subvariety of the variety of commutative residuated lattices, we study congruences of NPc-lattices and some subvarieties of NPc-lattices.

Much contemporary nanotoxicology, nanotherapeutic and nanoregulatory research has been characterised by a focus on investigating how delivery of engineered nanoparticles (ENPs) to cells is dictated primarily by components of the ENP surface. An alternative model, some implications of which are discussed here, begins with fundamental physicochemical research into the interaction of a dynamic nanoparticle-protein corona (NPC) with biological systems. The proposed new model also requires, however, that any such fresh NPC physicochemical research approach should involve integration and targeted collaboration from (...) the earliest stages with nanotoxicology, nanotherapeutics and nanoregulatory expertise. The justification for this integrated approach, we argue, relates not just to efficiency and promotion of innovation, but to an acknowledgement that public-funded basic physicochemical research in particular should now be accepted to incorporate strong higher order public goods elements from its inception, not merely after product development at the technology transfer stage. Issues, in other words, such as university research co-operation, commercialization and intellectual property (IP) protection, safety and cost-effectiveness regulatory assessment, as well as technology transfer should not be viewed as second tier considerations even in a ‘blue sky’ NPC basic research agenda. (shrink)

Since 1995, Public-Private Partnerships mode has been applied in mainland China accompanied by the issuance of a series of PPPs policies. Taking 201 policy documents promulgated from 1995 till 2019 as a research sample, this paper explores PPPs policy entity network change and policy learning behind it in China. Research results show the following: China’s PPPs policy entity network has mainly gone through three stages: partial-focus network with bad stability, loose-multiactor network with general stability, and balanced-multiactor network with good stability; (...) the key players are NPC in the first stage, MOF and NDRC in the second stage, and MOF and 8 other government entities in the third stage; policy learning behind PPPs policy entity network change is government learning in the first stage and lesson-drawing in the second and third stages. (shrink)

Transport through the nuclear pore complex (NPC), a keystone of the eukaryotic building plan, is known to involve a large channel and an abundance of phenylalanine–glycine (FG) protein domains serving as binding sites for soluble nuclear transport receptors and their cargo complexes. However, the conformation of the FG domains in vivo, their arrangement in relation to the transport channel and their function(s) in transport are still vividly debated. Here, we revisit a number of representative transport models—specifically Brownian affinity gating, selective (...) phase gating, reversible FG domain collapse, and reduction of dimensionality (ROD)—in the light of new data obtained by optical single transporter recording, optical superresolution microscopy, artificial nanopores, and many other techniques. The analysis suggests that a properly adapted, simplified version of the ROD model accounts well for the available data. This has implications for nucleocytoplasmic transport in general. (shrink)

The double membrane of the nuclear envelope is a formidable barrier separating the nucleus and cytoplasm of eukaryotic cells. However, movement of specific macromolecules across the nuclear envelope is critical for embryonic development, cell growth and differentiation. Transfer of molecules between the nucleus and cytoplasm occurs through the aqueous channel formed by the nuclear pore complex (NPC)Abbreviations: NPC, nuclear pore complex; GlcNac, N‐acetylglucosamine; WGA, wheat germ agglutinin. Although small molecules may simply diffuse across the NPC, transport of large proteins and (...) RNA requires specific transport signals and is energy dependent. A family of pore glycoproteins modified by O‐linked N‐acetylglucosamine moieties are essential for transport through the NPC. Recent evidence suggests that the regulation of nuclear transport may also involve the inteaction of RNA and nuclear proteins with specific binding proteins that recognize these transport signals. Are these nuclear pore glycoproteins and signal binding proteins the ‘gatekeepers’ that control access to the genetic material? Recent evidence obtained from a combination of biochemical and genetic approaches suggests – perhaps. (shrink)

The nuclear export of mRNA through the nuclear pore complex (NPC) is a process required for the healthy functioning of human cells, making it a critical area of research. However, the geometries of mRNA and the NPC are well below the diffraction limit of light microscopy, thereby presenting significant challenges in evaluating the discrete interactions and dynamics involved in mRNA nuclear export through the native NPC. Recent advances in biotechnology and single‐molecule super‐resolution light microscopy have enabled researchers to gain granular (...) insight into the specific contributions made by discrete nucleoporins in the nuclear basket of the NPC to the export of mRNA. Specifically, by expanding upon the docking step facilitated by the protein TPR in the nuclear basket as well as identifying NUP153 as being the primary nuclear basket protein initiating export through the central channel of the NPC. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:A View of Life:Nietzsche, Kierkegaard, and the NovelYi-Ping OngI"My general task," Nietzsche scrawled, in the margins of his own copy of Cervantes's Don Quixote: "to show how life philosophy and art can have a deeper and affinitive relationship with each other."1 This enigmatic inscription commands a second reading not only because it seems to articulate the thread that links many of Nietzsche's philosophical projects together, but also because of (...) the very book in which it appears. The book is not a lofty tome of Schopenhauer's philosophy, as might be expected, but a mere novel: a fact which suggests that the novel itself was the art form that precipitated reflection on the relation of art to what Nietzsche calls here "life philosophy." In this essay, my aim is to deepen critical understanding of the novel's influence on Nietzsche and Kierkegaard, the two philosophers who are widely considered the fathers of existentialism. By means of a comprehensive overview of the novelistic reading and writing of these thinkers, I will show that both Nietzsche and Kierkegaard were profoundly influenced by the literary form of the novel and by its techniques for representing consciousness, subjectivity, and worldview.My focus in the analysis that follows is on the question of why Nietzsche and Kierkegaard read novels, and not on the more specific question of what they gained from particular novels. Isolating form from theme has three main advantages. First, it elucidates an important aspect of the intellectual context for these philosophers that has received little scholarly attention, namely the issue of why Nietzsche and Kierkegaard were drawn to fictional novelistic prose and how this literary form [End Page 167] affected their philosophy. Second, it allows the "deeper... affinitive" relationship between existentialist philosophy and the novel form to emerge, revealing the way in which existentialism and realism in the novel share a distinctive stylistic approach to the understanding of lived experience. Finally, it illuminates an intellectual precedent for the work of later existentialist thinkers such as Heidegger, Sartre, Beauvoir, and Camus, who drew increasingly on novelistic forms as both vehicle and inspiration for their philosophy.There are no previous studies devoted entirely to the novels read by Nietzsche and Kierkegaard, despite the fact that Nietzsche lists Stendhal and Dostoevsky as two of the greatest influences upon his thinking and that Kierkegaard's first published work is the review of a novel. Why did Nietzsche read the works not only of "philosophical" novelists like Stendhal, Dostoevsky, and Tolstoy, but also of Eliot, Twain, Sterne, and Flaubert? Why did Kierkegaard's interest in the "life-view" of the individual crystallize through his reflections on Hans Christian Andersen's novel Only a Fiddler? How did both of these existentialist thinkers link the task of connecting life and philosophy with their reading of novels, and how is their reading of novels related to their attempt to write philosophy in novel and increasingly novelistic ways?These questions lead us to address anew the issue of how philosophy and literature are related in a way that is not simply thematic or allegorical. Furthermore, they ask us to take into account the importance of the novel to thinkers whose work has primarily been studied in the context of other "serious" philosophical texts, despite the stylistic and formal affinity of their work to the novels they read. As Thomas Brobjer points out in his recently published work on Nietzsche's reading habits and intellectual sources, Nietzsche's Philosophical Context: An Intellectual Biography (2008), none of the standard works on Nietzsche comment on his reading or library despite the fact that his private library has been more or less preserved in its entirety.2 Brobjer's work is the only large-scale study of Nietzsche's reading to date; however, it limits itself to "the philosophical influences on Nietzsche," even as it acknowledges that he "often was influenced by some who cannot conventionally be regarded as philosophers: by authors and literary critics" (NPC, p. 3). Although Brobjer mentions several of these authors and critics, even noting some of the marginalia found in these texts, he places them largely in the context of influences upon Nietzsche... (shrink)

The present work contains an axiomatic treatment of some parts of the restricted version of intuitionistic mathematics advocated by G. F. C. Griss, also known as negationless intuitionistic mathematics.Formal systems NPC, NA, and FIMN for negationless predicate logic, arithmetic, and analysis are proposed. Our Theorem 4 in Section 2 asserts the translatability of Heyting's arithmetic HAinto NA. The result can in fact be extended to a large class of intuitionistic theories based on HAand their negationless counterparts. For instance, in Section (...) 3 this is shown for Kleene's system of intuitionistic analysis FIMand our FIMN. (shrink)

The present work contains an axiomatic treatment of some parts of the restricted version of intuitionistic mathematics advocated by G. F. C. Griss, also known as negationless intuitionistic mathematics.Formal systems NPC, NA, and FIMN for negationless predicate logic, arithmetic, and analysis are proposed. Our Theorem 4 in Section 2 asserts the translatability of Heyting's arithmetic HAinto NA. The result can in fact be extended to a large class of intuitionistic theories based on HAand their negationless counterparts. For instance, in Section (...) 3 this is shown for Kleene's system of intuitionistic analysis FIMand our FIMN. (shrink)

Most documented extinctions of vertebrates in the last 400 years have been island endemics. In this paper, we focus on the need to develop a historical framework to establish conservation priorities for insular faunas and, in particular, to test the validity of nominal endemics. We use the example of the islands of the North Pacific Coast of North America, a region that includes approximately one-half of all mammals endemic to North American islands north of Mexico. Few of these endemics have (...) been re-evaluated since their original descriptions, although many of these islands have been heavily impacted by habitat conversion, species introductions, over-exploitation, and secondary ripple effects. Evidence from molecular genetics and paleontology suggests that many taxa arrived in the region since the last glacial advance. Some of these nominal endemics show minimal differentiation, while others comprise multiple evolutionary lineages. The NPC may also have played an important role in the in situ diversification of some taxa during the Pleistocene. Evidence, such as new fossil discoveries and numerous described endemics, lends support for refugia hypotheses. However, these ideas cannot be tested until a better understanding of geographic variation and the evolutionary relationships of the fauna and flora of the North Pacific Coast is developed. This framework would provide significant insight into the dynamic biogeographic history of the region and help prioritize conservation efforts. (shrink)

This article focuses on the role of the interchromatin compartment (IC) in shaping nuclear landscapes. The IC is connected with nuclear pore complexes (NPCs) and harbors splicing speckles and nuclear bodies. It is postulated that the IC provides routes for imported transcription factors to target sites, for export routes of mRNA as ribonucleoproteins toward NPCs, as well as for the intranuclear passage of regulatory RNAs from sites of transcription to remote functional sites (IC hypothesis). IC channels are lined by less‐compacted (...) euchromatin, called the perichromatin region (PR). The PR and IC together form the active nuclear compartment (ANC). The ANC is co‐aligned with the inactive nuclear compartment (INC), comprising more compacted heterochromatin. It is postulated that the INC is accessible for individual transcription factors, but inaccessible for larger macromolecular aggregates (limited accessibility hypothesis). This functional nuclear organization depends on still unexplored movements of genes and regulatory sequences between the two compartments. (shrink)

During brain development, neural precursor cells (NPCs) in different brain regions produce different types of neurons, and each of these regions plays a different role in the adult brain. Therefore, precise regionalization is essential in the early stages of brain development, and irregular regionalization has been proposed as the cause of neurodevelopmental disorders. The mechanisms underlying brain regionalization have been well studied in terms of morphogen‐induced expression of critical transcription factors for regionalization. NPC potential in different brain regions is defined (...) by chromatin structures that regulate the plasticity of gene expression. Herein, we present recent findings on the importance of chromatin structure in brain regionalization, particularly with respect to its regulation by Polycomb‐group proteins and chromatin accessibility. (shrink)

Philosophers and other thinkers have pondered tough questions about the nature of reality for thousands of years. Now, science seems to be discovering increasing support for this ancient concept, and Star Trek's holodeck technology offers great insights into understanding both old and new theories about what's real. The accumulation of data over the last twenty‐five years from a variety of scientific fields reveals that the reality seems to be holographic in nature. On the holodeck, there are two types of people: (...) players, like Data pretending to be Henry V or Sherlock Holmes, and non‐player characters (NPCs), holographic people created to interact with the players. Traditional mystical approaches offer the examples of prophets, saints, and saviors as similar to these holocharacters, with some traditions even providing teachings and techniques for individuals who seek to overcome their own holoprogramming. (shrink)

There are several types of characters in video games: the main protagonist/hero, the countless non-player characters (NPCs), and persistent non-player characters (PNPCs). While there is a substantial body of research about PNPCs from a game design point of view, they have been largely ignored by the academic community from a narrative perspective. The current essay aims to evaluate whether video game playing experience has an impact on a player’s reliance on the guidance of PNPCs in game play and if a (...) higher degree of experience enables a player to have a better appreciation for the narrative qualities of PNPCs as well as their complexity as characters. (shrink)

The relationship between kinetochores and nuclear pore complexes (NPCs) is intimate but poorly understood. Several NPC components and associated proteins are relocated to mitotic kinetochores to assist in different activities that ensure faithful chromosome segregation. Such is the case of the Mad1‐c‐Mad2 complex, the catalytic core of the spindle assembly checkpoint (SAC), a surveillance pathway that delays anaphase until all kinetochores are attached to spindle microtubules. Mad1‐c‐Mad2 is recruited to discrete domains of unattached kinetochores from where it promotes the rate‐limiting (...) step in the assembly of anaphase‐inhibitory complexes. SAC proficiency further requires Mad1‐c‐Mad2 to be anchored at NPCs during interphase. However, the mechanistic relevance of this arrangement for SAC function remains ill‐defined. Recent studies uncover the molecular underpinnings that coordinate the release of Mad1‐c‐Mad2 from NPCs with its prompt recruitment to kinetochores. Here, current knowledge on Mad1‐c‐Mad2 function and spatiotemporal regulation is reviewed and the critical questions that remain unanswered are highlighted. (shrink)

Although the capacity to infect non-dividing cells is a hallmark of lentiviruses, nuclear import is still barely understood. More than 100 research papers have been dedicated to this topic during the last 15 years, yet, more questions have been raised than answers. The signal-facilitating translocation of the viral preintegration complex (PIC) through the nuclear pore complex (NPC) remains unknown. It is clear, however, that nuclear import is the result of a complex interplay between viral and cellular components. In this review, (...) we discuss the current knowledge on nuclear import. We focus on the controversies and pitfalls and discuss the interplay between virus and host. (shrink)

The transactivation response‐DNA binding protein of 43 kDa (TDP‐43) is an aggregation‐prone nucleic acid‐binding protein linked to the etiology of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). These conditions feature the accumulation of insoluble TDP‐43 aggregates in the neuronal cytoplasm that lead to cell death. The dynamics between cytoplasmic and nuclear TDP‐43 are altered in the disease state where TDP‐43 mislocalizes to the cytoplasm, disrupting Nuclear Pore Complexes (NPCs), and ultimately forming large fibrils stabilized by the C‐terminal prion‐like (...) domain. Here, we review three emerging and poorly understood aspects of TDP‐43 biology linked to its aggregation. First, how post‐translational modifications in the proximity of TDP‐43 N‐terminal domain (NTD) promote aggregation. Second, how TDP‐43 engages FG‐nucleoporins in the NPC, disrupting the pore permeability and function. Third, how the importin α/β heterodimer prevents TDP‐43 aggregation, serving both as a nuclear import transporter and a cytoplasmic chaperone. (shrink)

This chapter explores the ethics of Robert Daly's actions in the episode “USS Callister”. We consider issues of privacy that relate to him stealing his co‐workers DNA in order to scan them into the game, as well as the ethics of how he treats the digital avatars of his co‐workers within the game. Examining Daly's actions from a few different approaches, we argue that Daly's actions towards his co‐workers avatars are very likely immoral, though ultimately we cannot know without knowing (...) Daly's thoughts. Finally, we end the chapter with some considerations relating to video games in general and the ways in which we must act when we play video games. (shrink)