bluuebunny/crossref_metadata_2025 huggingface dataset:
Caveolin targeting to late endosome/lysosomal membranes is induced by perturbations of lysosomal pH and cholesterol content
Authors: Mundy Dorothy I. , Li Wei Ping , Luby-Phelps Katherine , Anderson Richard G. W.
Published: January 2012

Caveolin-1 is an integral membrane protein of plasma membrane caveolae. Here we report that caveolin-1 collects at the cytosolic surface of lysosomal membranes when cells are serum starved. This is due to an elevation of the intralysosomal pH, since ionophores and proton pump inhibitors that dissipate the lysosomal pH gradient also trapped caveolin-1 on late endosome/lysosomes. Accumulation is both saturable and reversible. At least a portion of the caveolin-1 goes to the plasma membrane upon reversal. Several studies suggest that caveolin-1 is involved in cholesterol transport within the cell. Strikingly, we find that blocking cholesterol export from lysosomes with progesterone or U18666A or treating cells with low concentrations of cyclodextrin also caused caveolin-1 to accumulate on late endosome/lysosomal membranes. Under these conditions, however, live-cell imaging shows cavicles actively docking with lysosomes, suggesting that these structures might be involved in delivering caveolin-1. Targeting of caveolin-1 to late endosome/lysosomes is not observed normally, and the degradation rate of caveolin-1 is not altered by any of these conditions, indicating that caveolin-1 accumulation is not a consequence of blocked degradation. We conclude that caveolin-1 normally traffics to and from the cytoplasmic surface of lysosomes during intracellular cholesterol trafficking.
Cell-free reconstitution of vacuole membrane fragmentation reveals regulation of vacuole size and number by TORC1
Authors: Michaillat Lydie , Baars Tonie Luise , Mayer Andreas
Published: January 2012

Size and copy number of organelles are influenced by an equilibrium of membrane fusion and fission. We studied this equilibrium on vacuoles—the lysosomes of yeast. Vacuole fusion can readily be reconstituted and quantified in vitro, but it had not been possible to study fission of the organelle in a similar way. Here we present a cell-free system that reconstitutes fragmentation of purified yeast vacuoles (lysosomes) into smaller vesicles. Fragmentation in vitro reproduces physiological aspects. It requires the dynamin-like GTPase Vps1p, V-ATPase pump activity, cytosolic proteins, and ATP and GTP hydrolysis. We used the in vitro system to show that the vacuole-associated TOR complex 1 (TORC1) stimulates vacuole fragmentation but not the opposing reaction of vacuole fusion. Under nutrient restriction, TORC1 is inactivated, and the continuing fusion activity then dominates the fusion/fission equilibrium, decreasing the copy number and increasing the volume of the vacuolar compartment. This result can explain why nutrient restriction not only induces autophagy and a massive buildup of vacuolar/lysosomal hydrolases, but also leads to a concomitant increase in volume of the vacuolar compartment by coalescence of the organelles into a single large compartment.
De novo motif discovery facilitates identification of interactions between transcription factors in Saccharomyces cerevisiae
Authors: Chen Mei-Ju May , Chou Lih-Ching , Hsieh Tsung-Ting , Lee Ding-Dar , Liu Kai-Wei , Yu Chi-Yuan , Oyang Yen-Jen , Tsai Huai-Kuang , Chen Chien-Yu
Published: January 2012

Motivation: Gene regulation involves complicated mechanisms such as cooperativity between a set of transcription factors (TFs). Previous studies have used target genes shared by two TFs as a clue to infer TF–TF interactions. However, this task remains challenging because the target genes with low binding affinity are frequently omitted by experimental data, especially when a single strict threshold is employed. This article aims at improving the accuracy of inferring TF–TF interactions by incorporating motif discovery as a fundamental step when detecting overlapping targets of TFs based on ChIP-chip data.

Results: The proposed method, simTFBS, outperforms three naïve methods that adopt fixed thresholds when inferring TF–TF interactions based on ChIP-chip data. In addition, simTFBS is compared with two advanced methods and demonstrates its advantages in predicting TF–TF interactions. By comparing simTFBS with predictions based on the set of available annotated yeast TF binding motifs, we demonstrate that the good performance of simTFBS is indeed coming from the additional motifs found by the proposed procedures.

Contact:  hktsai@iis.sinica.edu.tw; chienyuchen@ntu.edu.tw

Supplementary information:  Supplementary data are available at Bioinformatics online.
MetExtract: a new software tool for the automated comprehensive extraction of metabolite-derived LC/MS signals in metabolomics research
Authors: Bueschl Christoph , Kluger Bernhard , Berthiller Franz , Lirk Gerald , Winkler Stephan , Krska Rudolf , Schuhmacher Rainer
Published: January 2012

Motivation: Liquid chromatography–mass spectrometry (LC/MS) is a key technique in metabolomics. Since the efficient assignment of MS signals to true biological metabolites becomes feasible in combination with in vivo stable isotopic labelling, our aim was to provide a new software tool for this purpose.

Results: An algorithm and a program (MetExtract) have been developed to search for metabolites in in vivo labelled biological samples. The algorithm makes use of the chromatographic characteristics of the LC/MS data and detects MS peaks fulfilling the criteria of stable isotopic labelling. As a result of all calculations, the algorithm specifies a list of m/z values, the corresponding number of atoms of the labelling element (e.g. carbon) together with retention time and extracted adduct-, fragment- and polymer ions. Its function was evaluated using native 12C- and uniformly 13C-labelled standard substances.

Availability: MetExtract is available free of charge and warranty at http://code.google.com/p/metextract/. Precompiled executables are available for Windows operating systems.

Contact:  rainer.schuhmacher@boku.ac.at

Supplementary information:  Supplementary data are available at Bioinformatics online.
A scalable and portable framework for massively parallel variable selection in genetic association studies
Authors: Chen Gary K.
Published: January 2012

Summary: The deluge of data emerging from high-throughput sequencing technologies poses large analytical challenges when testing for association to disease. We introduce a scalable framework for variable selection, implemented in C++ and OpenCL, that fits regularized regression across multiple Graphics Processing Units. Open source code and documentation can be found at a Google Code repository under the URL http://bioinformatics.oxfordjournals.org/content/early/2012/01/10/bioinformatics.bts015.abstract.

Contact:  gary.k.chen@usc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Feminist Theology and the Global Imagination
Authors: Jones Serene
Published: January 2012

This chapter presents an account of what feminist theology is and how it might help us understand and engage with our globalizing world. The first section provides a non-faith-specific definition of feminist theology as an intracultural activist enterprise aimed at exploring the landscape of religious imagination from a feminist perspective, and also lays out a few of feminist theology's most distinctive “plays of imagination.” The second section turns to faith-informed, Christian feminist theology, describing it as a more narrowly focused activist enterprise that explores the landscape of the distinctly Christian theological imagination from a feminist perspective. Its distinctive “plays of mind” are delineated as well. The third section turns to the topic of globalization and maps out the central features of “the global imagination,” describing the ways in which globalization has impacted and shifted our thinking processes in recent decades, particularly in the global North. The final section returns to Christian feminist theology (and to pluralistic feminist theology as well), suggesting ways its faith imagination—its theological plays of mind—might productively engage the global imagination with the aim of improving, in new and creative ways, the lives of women everywhere.
Gynocentric Thealogy of Tantric Hinduism: A Meditation Upon the Devi
Authors: Saxena Neela Bhattacharya
Published: January 2012

This chapter seeks to contribute to what Raimon Panikkar calls a dialogical dialogue, by speaking in the voice of a Shakta (Shakti worshipper) woman who grew up with the symbol of an all-powerful female deity: Kali, the presiding center of the Tantric tradition. Tantric Advaita, or non-dual thinking, and meditation practices permeate Indic traditions, making the world itself saturated with the spirit of the Divine Feminine. Tantric meditation upon the Devi that fine-tunes the entire being of the practitioner awakens her to the vibrant and subtle Shakti—the energy source of all which animates the universe—within her own body. This awakening at once annihilates the limited self bound by conditioned thinking and opens a window onto the infinite potentiality that only an encounter with death, symbolized by cremation-ground imagery of Kali, can inaugurate. The chapter presents this Gynocentric core of the Indic tradition within the larger context of Hinduism and its long, complex history. It shows how pluralist postmodern worldviews are more congenial to understanding polymorphous Hinduism(s) as opposed to absolutist Western perspectives influenced by imperial, missionary, and reductively rationalist ideas that misread the Great Goddess as a remnant of primitive religiosities, needing the light of masculine reason of Western Enlightenment. The chapter then locates the Indian context in a fast-changing world of global commerce that has the potential to impinge upon human diversity by imposing its own hegemonic vision. It further imagines a positive side effect of globalization—a new global consciousness strengthened by women's voices and spiritual convictions that would possibly herald what has been proclaimed as the second Axial age, opening up intercultural dialogues for the benefit of all—women, men, and the planet as a whole.
Globalization and Gender Inequality: A Contribution from a Latino Afro-feminist Perspective
Authors: López Maricel Mena
Published: January 2012

This chapter analyzes the context and daily life of Afro-Caribbean women within globalization in order to find ethnical praxis. This is prevailing and necessary in the actual social model where multiple social relations of power foment a civilization based on divisions and antagonism. The focus is on women registered not only within the globalized patriarchy, but also women that are being violated and discriminated against everywhere. When speaking about Latin American Afro-feminist theology, the author does not propose a sectarian and isolated movement, but affirms that a different world is possible. In the same manner, when she affirms the relatedness of our identity as women, she is conscious that, within black women, similar to rich, poor, young, old, lesbian, bisexual, and heterosexual women, there are differences. There are infinite identities, and this is why the chapter cannot become, in the end, an object of reflection; we cannot forget that our fight is also against our particular oppression. We must fight against patriarchy, domination, privileges, and control, as these are values that dehumanize us all.
Interrupting ‘Global-speak’: A Feminist Theological Response from Southern Africa to Globalization
Authors: Ackermann Denise M.
Published: January 2012

This chapter addresses two main questions: First, what critical issues raised by globalization in southern Africa will define the spaces for feminist theologies over the next decades? Second, how can a feminist theology that is attentive to its public voice and its interest in just and liberating praxis “interrupt” globalizing processes by offering alternative ways of addressing this complex reality? A few comments on the enigmas of using the term “southern Africa” are the starting point for addressing the first of these two questions. This is followed by comments on the multiple understandings of feminist theologies in this part of the world. Thereafter, the potential and the perils of globalization for women are discussed with reference to selected issues, such as employment, poverty, information technology, the environment, human rights, HIV and AIDS, and Christian attitudes. These issues are chosen as being pivotal to women's well-being, in fact to the well-being of all those for whom it is a daily struggle to survive. Turning to the second question, various features of a public feminist theology of praxis that can “interrupt” present “global-speak” and offer other ways of approaching globalization are described.
Feminist Theologies and the European Context
Authors: Isherwood Lisa
Published: January 2012

This chapter discusses three out of the many theologies in Europe addressing the question of globalization: indigenous theologies, and transcendence through developments in ecotheology and monotheism. It suggests that what is needed to hold back the advance of globalization is a solid sense of personhood rooted in cultural identity, but not so narrowly conceptualized as to be devoid of relational potential and respect for the rootedness of others. This is a significant challenge when the populations of the world are in such motion and we are forced to face the questions of: “How shall we sing the Lord's song in a strange land?” How shall we keep our sense of identity when everything is shifting around us? The global market, with its global “things,” can be a neat and easy answer for so many, but in fact it just adds to the sense of our non-being, our uprootedness, making us citizens of everywhere and nowhere—cheap and disposable like the commodities we so often buy. The importance of the person, the history, the belonging so central to authentic personhood can be so easily dislodged under the force of migration, even voluntary.
Globalization the Second Wave of Colonization: Impacts on wahine Māori
Authors: Cadigan Tui
Published: January 2012

Māori are the first nation people of Aotearoa New Zealand, a group of South West Pacific Islands. Colonized by the British Empire, Aotearoa came into being through an act consolidated by the signing of a controversial treaty between Māori tribes and Queen Victoria of England. From their earliest encounter, Māori women, or wahine Māori, experienced a dramatic shift in their social position. Traditionally, they occupied leadership roles at all levels of society. However, colonization instigated a societal reassignment that has led them to their current position behind white males, white females, white children, and Māori males, but ahead of Māori children. Key events in history contributed to the invisibility of wahine Māori in their own context and brought them to their present crisis. To assist the reader in understanding this context, this chapter first considers some key elements of Māori spirituality, and then explores developed and developing relationships, specifically the consequences of the differences between values systems of Māori and the British colonizer. The final section describes the current reality of wahine Māori and draws some conclusions about the influence of globalization in the process.
Feminist Theologies of a World Scripture(s) in the Globalization Era
Authors: Dube Musa W.
Published: January 2012

In the globalization era, justice-seeking feminist theologies are challenged to sharpen and reposition themselves to speak to the issues of the time by adopting new methods, topics, and frameworks. Consequently, “the boundaries of theology need to be redrawn in the light of the creation of new global cultures” and “crucial to the task of rewriting the story of feminist theology in the light of globalization is reflecting on the nature of a theological perspective it makes.” This chapter explores the interrelations of globalization, a world scripture (the Bible), and the vision of feminist theologies.
Theology and Identity in the Context of Globalization
Authors: Aquino María Pilar
Published: January 2012

Globalization, identity, and feminist theology have been the object of extensive academic research, and are perhaps the concepts that have had the greatest influence on our understanding of contemporary social reality and the function of religious rhetoric in today's world. In the theological field there has been a growing need to clarify the relationship between theology and identity formation in the current context of the social processes of “globalization.” This chapter explores the systematic interaction of these three concepts to bring to light the theological pertinence of a critical feminist theology of liberation for the visions and practices of social change. Such a theology develops the most appropriate analytical and hermeneutical frameworks to face the challenges raised by the current model of globalization, in the context of the social conditions created by which, a critical feminist theology functions as a religious ethical-political force of transformation for a new world of justice. The chapter is organized as follows. The first part highlights some methodological dimensions that expose the theological relevance of critical feminist liberation theology and its significance for present-day aspirations of social change. The second part addresses some key features of today's dominant model of society characterized by kyriarchal globalization, and points out their implications for feminist theological thought. The third and final part focuses on the social function of theological knowledge in the present circumstances and discusses some aspects that may shed light on possible future developments in feminist theology.
La Morenita on Skis: Women's Popular Marian Piety and Feminist Research on Religion
Authors: Vuola Elina
Published: January 2012

What do a skiing Virgin Mary in the snow-covered woods of Karelia and the dark-skinned Latin American Virgins, such as the Virgin of Guadalupe, La Morenita, have in common? This chapter takes examples from two different cultural contexts—Orthodox Karelia, the region between today's Russia and Finland, and parts of Latin America—for interpretations of the Virgin Mary as one who simultaneously shares and transcends women's often intimate everyday experiences, such as sexuality, childbirth, or the loss of a child. Aspects of (women's) popular devotion to the Virgin Mary both differ from official (especially Catholic) Mariology and, interestingly, coincide with some aspects of it, especially with the view of her symbolizing and transgressing the liminal space between the human and the divine. The examples are from different geographical areas and times, representing different fields of study and methods, such as theology, anthropology, and folklore studies, some using ethnographic methods, some textual.
Wittgenstein Reads Russell
Authors: Landini Gregory
Published: January 2012

Bertrand Russell and Ludwig Wittgenstein both left voluminous work notes and letters and they knew a great many people — statesmen, poets, academicians, lovers, and friends — who themselves wrote memoirs. Russell regarded Wittgenstein as a protégé and did much to establish a career for him. He secured the publications of Wittgenstein's oracular and unorthodox Tractatus Logico-Philosophicus. He presided over the Viva which accepted Tractatus as a dissertation for Wittgenstein's Ph.D. degree (1929). Two theses have dominated the understanding of Russell's philosophy. First, in Principia Mathematica, Russell advanced a ramified type-theory of entities. Second, Russell's logical atomism is a form of reductive empiricistic epistemology. With the help of the volumes of manuscripts that Russell left, it now appears that both are false. In later years, Russell described his thoughts on the philosophy of logic and mathematics as a reluctant ‘retreat from Pythagoras’. Wittgenstein's Tractatus certainly did not intend to surrender logic to psychology, conventionalism, naturalism, or any empirical science.
Wittgenstein On Mathematics
Authors: Potter Michael
Published: January 2012

The philosophy of mathematics was one of Ludwig Wittgenstein's central concerns from the beginning of his philosophical career until close to the end: it is one of the issues addressed in Tractatus Logico-Philosophicus. When Wittgenstein returned to philosophy and to Cambridge in 1929, it was the problem of the infinite that he started to consider — first of all in concert with Frank Ramsey. As far as one can judge, Wittgenstein and Ramsey seem to have moved together towards finitism, that is, a rejection of the extensional view of generalisation in the case of infinitely many propositions. Wittgenstein deduces that the sense of an arithmetical generalisation is its inductive proof. In addition, Wittgenstein argues that there is no problem of inconsistency until we actually find an inconsistency. He attributes the existence of hidden contradictions to ambiguity in the rules. As early as 1930, Wittgenstein was explicit about the ‘unbridgeable gulf between rule and application’, which is the essence of the rule-following argument.
Wittgenstein On Surveyability of Proofs
Authors: Marion Mathieu
Published: January 2012

Philosophers of mathematics are often divided between ‘mainstream’ and ‘maverick’. Ludwig Wittgenstein could hardly be classified as ‘mainstream’. He had in common with other ‘mavericks’, however, a critical stance towards the value of the ‘mainstream’ philosophy of mathematics of his days, mostly but not only as he knew it from the logicist tradition of Gottlob Frege, Bertrand Russell, Frank Ramsey, and Rudolf Carnap. Wittgenstein's remarks on the ‘Übersichtlichkeit’ or ‘surveyability’ of proofs were read as forming part of an argument in support of a radical ‘anti-realist’ account of mathematics, which coincides with ‘strict finitism’ in the foundations of mathematics. This article argues that Wittgenstein's ‘surveyability argument’ is best understood not as an argument concerning the length of proofs but as involving the recognition that formal proofs possess a non-eliminable visual element, neglected by Russell. It also discusses the consequences that Wittgenstein drew from his argument, especially as they relate to the larger issue of the cogency of mathematical ‘explicativism’.
From Logical Method to ‘Messing About’: Wittgenstein on ‘Open Problems’ in Mathematics
Authors: Säätelä Simo
Published: January 2012

David Hilbert claimed that all mathematical problems can be solved. While Ludwig Wittgenstein agrees, he also wants to distinguish between different uses of the word ‘problem’. ‘Open problems’ in mathematics are often understood as being expressed by mathematical propositions that are undecided in the sense that they are not known to be provable or disprovable within currently accepted systems of mathematics. Wittgenstein thinks, controversially, that it is nonsensical to treat such ‘propositions’ as genuine mathematical propositions. On the other hand, he does not want to claim that it is illegitimate for mathematicians to concern themselves with problems such as Goldbach's conjecture, or Fermat's last theorem. This article explores the way Wittgenstein dealt with these issues in the early 1930s, focusing on his treatment of Fermat's theorem. It also looks at how Wittgenstein's treatment of these issues reflects a development towards a less dogmatic view of what is involved in mathematicians' claims to understand such ‘propositions’, which is an important part of the development of his philosophical views from the ‘middle’ to the ‘late’ philosophy.
The Life of The Sign
Authors: Minar Edward
Published: January 2012

Groping for direction in the midst of his investigation of rule-following in Philosophical Investigations, Ludwig Wittgenstein remarks: ‘Language is a labyrinth of paths. You approach from one side and know your way about; you approach the same place from another side and no longer know your way about’. This article examines Wittgenstein's conception of philosophy, his methods, and the instructions he provides for our use of his ‘album’ of ‘sketches’. It examines some features of how agreement functions in Wittgenstein's treatment of rule-following by working toward an interpretation of his apparently climactic conclusion in Investigations: ‘If language is to be a means of communication there must be agreement not only in definition but also (queer as this may sound) in judgments. This seems to abolish logic, but does not do so’. To locate the significance of agreement in the practice of rule-following, this article looks at Wittgenstein's remarks about ‘the life of the sign’, a theme from the outset of the Investigations.
Meaning and Understanding
Authors: Stroud Barry
Published: January 2012

Almost from the beginning of his return to philosophy in Cambridge in 1929, Ludwig Wittgenstein was concerned not only with the relation of sentences or propositions to reality but also with the idea of someone's thinking or meaning or understanding something in a particular way. He also returned to the idea of a ‘limit’, this time to ‘the limit of language’. In the early parts of Philosophical Grammar, Wittgenstein takes up the question of how one can talk about ‘understanding’ or ‘not understanding’ a sentence. The implications of middle-period reflections on the impossibility of understanding language and meaning ‘from outside’ are illustrated and developed at many points and in many ways throughout Philosophical Investigations. Wittgenstein's remark that it is impossible to describe the fact that corresponds to a sentence without simply repeating the sentence is immediately followed by the observation that ‘this has to do with the Kantian solution of the problem of philosophy’.
Wittgenstein and Idealism
Authors: Cerbone David R.
Published: January 2012

Of the many sources of interpretive conflict in Ludwig Wittgenstein's philosophy, one of the most recalcitrant is the question of his philosophy's ultimate commitment to idealism. Those who argue that Wittgenstein must in the end be some kind of idealist will cite, among other things, his appeal to ‘forms of life’ (either as diverse or ultimately and emphatically singular), his attention to the (alleged) constitutive role of, variously, our practices, community, or ‘mindedness’ in the formation of concepts, and his apparent dismissal of philosophical problems and questions as instances of speaking ‘outside’ of language-games. That just these features of Wittgenstein's philosophy converge to make for an ultimately idealist philosophy is succinctly summarised in Thomas Nagel's characterisation. Nagel, who labels Wittgenstein ‘one of the most important sources of contemporary idealism’, traces this influence to his views on ‘the conditions of meaning’.
Wittgenstein on The First Person
Authors: Child William
Published: January 2012

Questions about the self, the use of ‘I’, and the first-person point of view arise throughout Ludwig Wittgenstein's writings. This article explores two interrelated issues. First, what is the function and significance of the first-person pronoun? Second, what is the relation between the first-person point of view — the point of view that each of us has on ourselves, our experiences, and our mental states — and the second- or third-person point of view — the point of view we adopt towards others, their experiences, and their mental states? When ‘I’ is used ‘as object’, Wittgenstein says, ‘the possibility of an error has been provided for’; when ‘I’ is used ‘as subject’, ‘no error is possible’. Wittgenstein has identified a genuine feature of certain self-ascriptions: immunity to error through misidentification. One of Wittgenstein's aims in Philosophical Investigations is to offer an account of the ‘language-game’ of ascribing sensations and attitudes to oneself and others that does justice to both first-person and third-person aspects of the mental, while avoiding the twin extremes of Cartesian introspectionism, on the one hand, and behaviourism, on the other.
Private Experience and Sense Data
Authors: Snowdon Paul
Published: January 2012

In the mid 1930s, Ludwig Wittgenstein was immersed in problems about, amongst other things, experience, or perhaps one might say, our thought about experience. One record of his developing thinking are the notes that Rush Rhees himself made of the lectures by Wittgenstein on these topics which Rhees attended in 1936, published under the title ‘The Language of Sense Data and Private Experience’, in Philosophical Occasions. The ideas that Wittgenstein is developing in these notes and lectures culminated in the discussion of the same topics in Philosophical Investigations. What views about sense data and private experience is Wittgenstein proposing? Wittgenstein suggests that bad philosophy is produced by the ‘bewitchment of intelligence by language’. In addition, he brings out a genuine contrast between the status of the idea of the private object account of perception and the idea of private objects as involved in the experience of sensations. It is natural to read Wittgenstein's brief discussion of the so-called ‘visual room’ in Philosophical Investigations as another engagement with the sense datum model of perception.
Privacy
Authors: Schulte Joachim
Published: January 2012

In his Philosophical Investigations, Ludwig Wittgenstein does very little to explain what he means by ‘private’. To illustrate Wittgenstein's willingness to combine the adjective ‘private’ with all kinds of nouns, this article gives a list of such nouns based on his ‘Notes for Lectures on Private Experience’ and ‘Sense Data’: definition, experience, game of chess, impression, justification, language, language game, memory, personal experience, sensation, sense data, visual image. Items like justification, definition, and the game of chess are not covered by ‘experiences’, while impressions, sensations, and visual images are probably meant to fall under this heading. Objectivity is one idea that Wittgenstein contrasts with privacy. And objectivity, he suggests, presupposes that the people concerned use a language in the minimal sense of making recognizably regular use of what we can conceive of as symbols. The idea of an inner world as well as all those notions connected with it form only part of what Wittgenstein is driving at when he uses the word ‘private’ in relevant contexts.
Action and The Will
Authors: Hyman John
Published: January 2012

In Philosophical Investigations, Ludwig Wittgenstein talks about action and the will. The main ideas we need to be acquainted with in order to understand Wittgenstein's remarks on this topic are, first, Arthur Schopenhauer's neo-Kantian theory of the will, which Wittgenstein seems to have fully accepted in 1916, and which still influenced his thinking in 1947, and second, the theory advanced in William James's The Principles of Psychology, which Wittgenstein encountered in the 1930s, and rejected root and branch. Schopenhauer and James were in turn reacting, in very different ways, to the empiricist theory of the will, which received its classic exposition in John Locke's Essay Concerning Human Understanding. This article argues that Wittgenstein's treatment of action and the will in Philosophical Investigations is seriously flawed. Wittgenstein fails to disentangle the active/passive distinction and the voluntary/not voluntary distinction; he fails to see that voluntariness is not only an attribute of activity, but of passivity as well; and he confuses action and motion.
Wittgenstein on Scepticism
Authors: Pritchard Duncan
Published: January 2012

The problem of scepticism informs all of Ludwig Wittgenstein's writing, from the remarks on solipsism in Tractatus Logico-Philosophicus to his final notebooks dealing with G. E. Moore's famous commonsense response to scepticism, published as On Certainty. Wittgenstein offers a picture of the structure of reasons that is the very picture that we ordinarily employ, at least when we are not in the grip of the alternative philosophical picture which the sceptic employs. Wittgenstein refers to hinges as propositions throughout On Certainty. The proponent of the non-propositional view has a fairly stiff exegetical task on her hands. A less radical form of non-epistemicism which avoids this difficulty holds that while hinges are indeed propositions, they are not fact-stating propositions but rather express norms. According to contextualism, the hinges are known just so long as one does not enter a context where such hinges are brought into question. It would seem that Wittgenstein's approach to scepticism has important ramifications for contemporary epistemology even if it is set within an externalist framework.
Grammar in the Philosophical Investigations
Authors: McGinn Marie
Published: January 2012

Ludwig Wittgenstein describes the kind of investigation he is engaged in Philosophical Investigations as ‘a grammatical one’. He speaks of looking for ‘grammatical differences’ and of ‘the rules of grammar’; and he makes a distinction between the ‘surface grammar’ of a word and its ‘depth grammar’. He traces the misunderstandings which he holds to lie at the root of philosophical problems and paradoxes to ‘grammatical illusions’, and to the creation of ‘grammatical fictions’. It is clear that he places the concept of grammar and of grammatical investigation at the heart of his understanding of the aims and methods of his later philosophy. Understanding what he means by the terms ‘grammar’, ‘depth grammar’, and ‘grammatical investigation’ is therefore fundamental to an understanding of the Investigations. It is possible that a perspicuous representation is concerned with a dimension of use that focuses on how speakers operate with words. Moreover, Wittgenstein has been interpreted as aiming to clarify the use of the concepts of understanding, meaning, and thinking.
Aspect Perception and Philosophical Difficulty
Authors: Baz Avner
Published: January 2012

This article traces a new line of thought through, or actually to, Ludwig Wittgenstein's writings on aspect perception. Its point of bearing is the second part of the Brown Book. It show that the trail of philosophical reflection that apparently naturally leads Wittgenstein in the Brown Book from questions concerning how we ought to conceive of our various mental states (and processes) — that is, from what is arguably one of the underlying overall concerns of the first part of Philosophical Investigations — to the topic of aspect perception, is in fact philosophically interesting. It is also different from what previous attempts to relate the remarks on aspects to the first part of the Investigations would have made one expect. An important point of departure for Wittgenstein's work was that he found literally incredible the dominating conception of philosophy. This article explores aspect perception, aspect-blindness, and philosophical difficulty. It discusses the ‘illusion’ or ‘delusion’ that Wittgenstein detects in those moments in which we attend to instances of Φing in order to find out what Φing is.
Wittgenstein and The Moral Dimension of Philosophical Problems
Authors: Backström Joel
Published: January 2012

Ludwig Wittgenstein's so-called Big Typescript from the early 1930s includes a famous chapter on ‘Philosophy’. This article examines how Wittgenstein saw the character of the philosophical problems he was dealing with, in particular the connection between them, language trouble, and the broadly speaking moral-existential difficulties apparently referred to in the opening statement. It is crucial to realise that reflection on the possible intertwining of philosophical problems and moral difficulties will not only challenge standard conceptions of philosophy, but also of morality. Wittgenstein always stresses the ‘depth’ of philosophical problems. Through his patient work of reflection and questioning of philosophical preconceptions and prejudices, he reveals how difficult it is, not just to free oneself from their grip but to realise that one is in their grip.
Wittgenstein on Religious Belief
Authors: Mulhall Stephen
Published: January 2012

This article is based on three assumptions. The first is that Ludwig Wittgenstein's impact in the philosophy of religion has been more a function of the work of those inspired by him than of his own writings on this topic. The second is that Wittgensteinian philosophers of religion took their primary inspiration from Wittgenstein's later approach to philosophy in general, as manifest in the Philosophical Investigations, rather than from his specific writings on religion. The third assumption is that such Wittgensteinian philosophy of religion has been burdened virtually from its outset by the fateful charge of fideism. This charge originated with Kai Nielsen, who argued that assumptions common to a range of Wittgensteinian authors entailed an unacceptable immunisation of religious belief against rational criticism (just as theological fideists hold that religious belief is grounded on faith rather than reason). This article also explores Cora Diamond's development and application of a third perspective known as ‘The Realistic Wittgenstein’, in addition to the first two: ‘The Fideist Wittgenstein’ and ‘The Canonical Wittgenstein’.
Wittgenstein on Aesthetics
Authors: Budd Malcolm
Published: January 2012

Ludwig Wittgenstein had a deep and enduring interest in at least two of the major art forms: literature and music. He practised, if only briefly, two others: architecture and sculpture. In truth, art did not lie at the centre of Wittgenstein's philosophical concerns. Nevertheless, it is precisely because he held the finest art in such high esteem, assigning to it an absolute value, that it eludes the net of language as articulated in Tractatus Logico-Philosophicus, and he confessed that because it was impossible for him to say in Philosophical Investigations one word about all that music had meant in his life, it would be difficult for him to be understood. Tractatus has only a single gnomic remark about aesthetics: ‘Ethics and aesthetics are one’. In his lectures, Wittgenstein makes a number of claims about the concept of beauty, some of which appear also in his published writings. In his later philosophy, Wittgenstein's thoughts about aesthetics appear to have been focused almost exclusively upon art, issues in the aesthetic appreciation of nature not appearing to engage him.
Modelling the lymphatic system: challenges and opportunities
Authors: Margaris K. N. , Black R. A.
Published: January 2012

The lymphatic system is a vital part of the circulatory and immune systems, and plays an important role in homeostasis by controlling extracellular fluid volume and in combating infection. Nevertheless, there is a notable disparity in terms of research effort expended in relation to the treatment of lymphatic diseases in contrast to the cardiovascular system. While similarities to the cardiovascular system exist, there are considerable differences in their anatomy and physiology. This review outlines some of the challenges and opportunities for those engaged in modelling biological systems. The study of the lymphatic system is still in its infancy, the vast majority of the models presented in the literature to date having been developed since 2003. The number of distinct models and their variants are few in number, and only one effort has been made thus far to study the entire lymphatic network; elements of the lymphatic system such as the nodes, which act as pumps and reservoirs, have not been addressed by mathematical models. Clearly, more work will be necessary in combination with experimental verification in order to progress and update the knowledge on the function of the lymphatic system. As our knowledge and understanding of its function increase, new and more effective treatments of lymphatic diseases are bound to emerge.
Statistical modelling of ground temperature in mountain permafrost
Authors: Blanchet J. , Davison A. C.
Published: January 2012

Permafrost consists of soil and rocks that remain at 0
°
C or below for at least two consecutive years. In mountains, permafrost ground ice acts like cement, stabilizing rock walls. Its degradation, following climate warming, may lead to slope instability in high mountains and damage to infrastructure, so knowledge about its evolution is essential for risk analysis. In pure solids, heat is transferred by conduction, but permafrost ground is also subject to non-conductive fluxes, and heat transfers are influenced by factors such as air temperature and snow cover, so a deterministic scheme cannot fully describe heat propagation. Current approaches to modelling use numerical models involving heat conduction schemes and energy balance models, requiring data on quantities such as relative humidity and radiation. We describe a stochastic treatment of the heat equation, which adapts to space–time changes in heat transfers driven by factors such as air temperature and snow cover, without requiring corresponding data, as part of a statistical model. The flexibility and performance of our approach are illustrated using data from two boreholes in the Swiss Alps, which show the strong influence of snow cover on ground temperature and the long-term degradation of permafrost produced by the 2003 heat wave.
Role of enhancin in Mamestra configurata nucleopolyhedrovirus virulence: selective degradation of host peritrophic matrix proteins
Authors: Toprak Umut , Harris Stephanie , Baldwin Douglas , Theilmann David , Gillott Cedric , Hegedus Dwayne D. , Erlandson Martin A.
Published: January 2012

To infect per os, baculovirus virions cross the peritrophic matrix (PM) to reach the midgut epithelium. Insect intestinal mucins (IIMs) are PM proteins that protect the PM and aid passage of the food bolus through the gut. Some baculoviruses, including Mamestra configurata nucleopolyhedrovirus (MacoNPV-A), encode metalloproteases, known as enhancins, that facilitate infection by degrading IIMs. We examined the interaction between MacoNPV-A enhancin and M. configurata IIMs both in vivo and in vitro. Per os inoculation of M. configurata larvae with MacoNPV-A occlusion bodies (OBs) resulted in the degradation of McIIM4 within 4 h of OB ingestion, while McIIM2 was unaffected. The PM recovered by 8 h post-inoculation. To investigate whether enhancin was responsible for the degradation of IIM, a recombinant Autographa californica multiple nucleopolyhedrovirus expressing MacoNPV enhancin (AcMNPV-enMP2) was constructed. Enhancin was found to be a component of occlusion-derived virions in AcMNPV-enMP2 and MacoNPV-A. In in vitro assays, McIIM4 was degraded after MacoNPV-A and AcMNPV-enMP2 treatments. Degradation of McIIM4 was inhibited by EDTA, a metalloprotease inhibitor, indicating that the degradation was due to enhancin activity. Thus, MacoNPV-A enhancin is able to degrade major structural PM proteins, but exhibits target substrate specificity.
Binding of cellular p32 protein to the rubella virus P150 replicase protein via PxxPxR motifs
Authors: Suppiah Suganthi , Mousa Heather A. , Tzeng Wen-Pin , Matthews Jason D. , Frey Teryl K.
Published: January 2012

A proline-rich region (PRR) within the rubella virus (RUBV) P150 replicase protein that contains three SH3 domain-binding motifs (PxxPxR) was investigated for its ability to bind cell proteins. Pull-down experiments using a glutathioneS-transferase–PRR fusion revealed PxxPxR motif-specific binding with human p32 protein (gC1qR), which could be mediated by either of the first two motifs. This finding was of interest because p32 protein also binds to the RUBV capsid protein. Binding of p32 to P150 was confirmed and was abolished by mutation of the first two motifs. When mutations in the first two motifs were introduced into a RUBV cDNA infectious clone, virus replication was significantly impaired. However, virus RNA synthesis was found to be unaffected, and subsequent immunofluorescence analysis of RUBV-infected cells revealed co-localization of p32 and P150 but little overlap of p32 with RNA replication complexes, indicating that p32 does not participate directly in virus RNA synthesis. Thus, the role of p32 in RUBV replication remains unresolved.
Inhibition of infectious bursal disease virus infection by artificial microRNAs targeting chicken heat-shock protein 90
Authors: Yuan Weifeng , Zhang Xinyu , Xia Xiaoli , Sun Huaichang
Published: January 2012

Infectious bursal disease virus (IBDV) causes an important disease in young chickens. Chicken heat-shock protein 90 (cHsp90) has been shown to be a functional component of the cellular receptor complex for IBDV infection. This study demonstrates the inhibitory effect of vector-expressed anti-cHsp90α microRNA (miRNA) on IBDV infection. The reporter vectors pcHsp90α-EGFP and pcHsp90β-EGFP were constructed to facilitate effective miRNA selection. Two anti-cHsp90α and one anti-cHsp90β miRNA-expression vectors were constructed for a stable transfection study. Poly(A)-tailed RT-PCR detected sequence-specific miRNA transcription in transfected cells. Semiquantitative RT-PCR showed inhibition of cHsp90 transcription in transfected cells. A virus-titration assay showed that the anti-cHsp90α miRNA, but not the anti-cHsp90β miRNA, had inhibitory effects on IBDV infection. These results suggest that cHsp90α is a functional component of the cellular receptor complex for IBDV infection, and that anti-cHsp90α miRNA could be used as an anti-IBDV reagent.
Cancer Surgery in the Elderly
Authors: Kowdley Gopal C. , Merchant Nishant , Richardson James P. , Somerville Justin , Gorospe Myriam , Cunningham Steven C.
Published: January 2012

The proportions both of elderly patients in the world and of elderly patients with cancer are both increasing. In the evaluation of these patients, physiologic age, and not chronologic age, should be carefully considered in the decision-making process prior to both cancer screening and cancer treatment in an effort to avoid ageism. Many tools exist to help the practitioner determine the physiologic age of the patient, which allows for more appropriate and more individualized risk stratification, both in the pre- and postoperative periods as patients are evaluated for surgical treatments and monitored for surgical complications, respectively. During and after operations in the oncogeriatric populations, physiologic changes occuring that accompany aging include impaired stress response, increased senescence, and decreased immunity, all three of which impact the risk/benefit ratio associated with cancer surgery in the elderly.
Pulsed Wave Doppler Ultrasound Is Useful to Assess Vasomotor Response in Patients with Multiple System Atrophy and Well Correlated with Tilt Table Study
Authors: Chang Ke-Vin , Chen Wen-Shiang , Wu Ruey-Meei , Chen Ssu-Yuan , Shen Hsiu-Yu , Lan Ching , Wang Yen-Ho
Published: January 2012

The study aim was to assess sympathetic vasomotor response (SVR) by using pulsed wave Doppler (PWD) ultrasound in patients with multiple system atrophy (MSA) and correlate with the tilt table study. We recruited 18 male patients and 10 healthy men as controls. The SVR of the radial artery was evaluated by PWD, using inspiratory cough as a provocative maneuver. The response to head-up tilt was studied by a tilt table with simultaneous heart rate and blood pressure recording. The hemodynamic variables were compared between groups, and were examined by correlation analysis. Regarding SVR, MSA patients exhibited a prolonged latency and less heart rate acceleration following inspiratory cough. Compared with the tilt table test, the elevation of heart rate upon SVR was positively correlated to the increase of heart rate after head-up tilt. The correlation analysis indicated that the magnitude of blood pressure drop from supine to upright was positively associated with the SVR latency but negatively correlated with the heart rate changes upon SVR. The present study demonstrated that blunted heart rate response might explain MSA's vulnerability to postural challenge. PWD may be used to predict cardiovascular response to orthostatic stress upon head-up tilt in MSA patients.