RFID tags, small microchips no bigger than grains of rice, are currently being embedded in product labels, clothing, credit cards, and the environment, among other sites. Activated by the appropriate receiver, they transmit information ranging from product information such as manufacturing date, delivery route, and location where the item was purchased to (in the case of credit cards) the name, address, and credit history of the person holding the card. Active RFIDs have the capacity to transmit data without having to (...) be activated by a receiver; they can be linked with embedded sensors to allow continuous monitoring of environmental conditions, applications that interest both environmental groups and the US military. The amount of information accessible through and generated by RFIDs is so huge that it may well overwhelm all existing data sources and become, from the viewpoint of human time limitations, essentially infinite. What to make of these technologies will be interrogated through two contemporary fictions, David Mitchell's Cloud Atlas and Philip K. Dick's Ubik. Cloud Atlas focuses on epistemological questions — who knows what about whom, in a futuristic society where all citizens wear embedded RFID tags and are subject to constant surveillance. Resistance takes the form not so much of evasion (tactical moves in a complex political Situation) but rather as a struggle to transmit information to present and future stakeholders in a world on the brink of catastrophe. Ubik, by contrast, focuses on deeper ontological questions about the nature of reality itself. Both texts point to the necessity to reconceptualize information as ethical action embedded in contexts and not merely as a quantitative measure of probabilities. (shrink)

An awareness of the significance of location in the production and dissemination of scientific knowledge has brought a new dimension to recent work on the sociology of science. But the importance of speech in scientific enterprises has been less well developed. This article explores the idea of `spaces of speech' by underscoring the connections between location and locution. It develops a case study of how Darwinian evolution was talked about in different sites using examples from Ireland and the American South (...) during the latter part of the 19th century. These reveal how sites enable and constrain what may be said, and heard, about particular scientific claims, and how they are crucial to understanding the circulation of scientific claims in public arenas. (shrink)

The idea of the “Active education” means the opportunity for children to study the surrounding world not only by textbooks or with the help of the sites in the INTERNET (a rather passive action) but also by a direct contact with this world via its active investigation and solution of some concrete problems.This may be the study of environmental contamination and other modern practical ecological problems such as the transformation of the agriculture production resulting from climatic variations or anthropogenic changes (...) of landscapes. (shrink)

A central concern of the cognitive science of language since its origins has been the concept of the linguistic system. Recent approaches to the system concept in language point to the exceedingly complex relations that hold between many kinds of interdependent systems, but it can be difficult to know how to proceed when “everything is connected.” This paper offers a framework for tackling that challenge by identifying *scale* as a conceptual mooring for the interdisciplinary study of language systems. The paper (...) begins by defining the scale concept—simply, the possibility for a measure to be larger or smaller in different instances of a system, such as a phonemic inventory, a word's frequency value in a corpus, or a speaker population. We review sites of scale difference in and across linguistic subsystems, drawing on findings from linguistic typology, grammatical description, morphosyntactic theory, psycholinguistics, computational corpus work, and social network demography. We consider possible explanations for scaling differences and constraints in language. We then turn to the question of *dependencies between* sites of scale difference in language, reviewing four sample domains of scale dependency: in phonological systems, across levels of grammatical structure (Menzerath's Law), in corpora (Zipf's Law and related issues), and in speaker population size. Finally, we consider the implications of the review, including the utility of a scale framework for generating new questions and inspiring methodological innovations and interdisciplinary collaborations in cognitive-scientific research on language. (shrink)

Two recently published inscriptions afford new insights into this subject. They were published separately and independently within a year or two of one another. Much is now to be gained by considering them together. The first inscription, found at Philippi in 1936, published by C. Vatin in Proc. 8th Epigr. Conf. , 259–70, and published with a fuller commentary by L. Missitzis in The Ancient World 12 , 3–14, records the decision by Alexander the Great on the use of lands (...) given by his father, Philip II, and in some cases confirmed by himself. The second inscription, found at the site of ancient Kalindoia in 1982, was published with exemplary speed and an excellent commentary by I. P. Vokotopoulou in Ancient Macedonia 4 , 87–114. It records the names of the priests of Asclepius on a stele dedicated to Apollo; and in the preamble it mentions the name of Alexander, being Alexander the Great. Philippi and Kalindoia were both within the limits of the kingdom of Philip and Alexander. (shrink)

Although there has long been a division in studies of consciousness between a focus on neuronal processes or conversely an emphasis on the ruminations of a conscious self, the long-standing split between mechanism and meaning within the brain was mirrored by a split without, between information as a technical term and the meanings that messages are commonly thought to convey. How to heal this breach has posed formidable problems to researchers. Working through the history of cybernetics, one of the historical (...) sites where Claude Shannon’s information theory quickly became received doctrine, we argue that the cybernetic program as it developed through second-order cybernetics and autopoietic theory remains incomplete. In this article, we return to fundamental questions about pattern and noise, context and meaning, to forge connections between consciousness, narrative and media. The thrust of our project is to reintroduce context and narrative as crucial factors in the processes of meaning-making. The project proceeds along two fronts: advancing a theoretical framework within which context plays its properly central role; and demonstrating the importance of context by analyzing two fictions, Stanislaw Lem’s His Master’s Voice and Joseph McElroy’s Plus, in which context has been deformed by being wrenched away from normal human environments, with radical consequences for processes of meaning-making. (shrink)

This commentary builds on Haico te Kulve and Arie Rip’s ( 2011 ) notion of “engagement agents,” individuals that must be able to move between multiple dimensions, or “levels” of research, innovation, and policy processes. The commentary compares and contrasts the role of the engagement agent within the Constructive Technology Assessment and integration approaches, and suggests that on-site integration research represents one way to transform both social and natural scientists into competent and informed “engagement agents,” a new generation of (...) researchers that possess the knowledge and capacities to forge “novel linkages” between the oftentimes disparate terrains of science, politics, and policy. (shrink)

Social media and Internet technologies present several emerging and ill-explored issues for a modern healthcare workforce. One issue is patient-targeted Googling, which involves a healthcare professional using a social networking site or publicly available search engine to find patient information online. The study’s aim was to address a deficit in data and knowledge regarding PTG, and to investigate medical student use of SNSs due to a close association with PTG. The authors surveyed final year medical students at the Otago (...) Medical School, University of Otago in January 2016. A subset completed focus groups that were analysed using thematic analysis to identify key themes relating to students’ attitudes towards PTG, and reasons why they might engage in PTG. Fifty-four students completed the survey, which showed that PTG was uncommon. Attitudes were varied and context dependent. Most participants saw problems with PTG and favoured more explicit guidance on the issue. SNS usage was high ; participants were concerned by the content of their SNS profiles and who they were connecting with online. Participants showing high SNS use were 1.83 times more likely to have conducted PTG than lower use groups. The diverse attitudes uncovered in this study indicated that teaching or guidelines could be useful to healthcare professionals considering PTG. Though ethically problematic, PTG may be important to patient care and safety. The decision to conduct PTG should be made with consideration of ethical principles and the intended use of the information. (shrink)

Background Social media and Internet technologies present several emerging and ill-explored issues for a modern healthcare workforce. One issue is patient-targeted Googling, which involves a healthcare professional using a social networking site or publicly available search engine to find patient information online. The study’s aim was to address a deficit in data and knowledge regarding PTG, and to investigate medical student use of SNSs due to a close association with PTG. Method The authors surveyed final year medical students at (...) the Otago Medical School, University of Otago in January 2016. A subset completed focus groups that were analysed using thematic analysis to identify key themes relating to students’ attitudes towards PTG, and reasons why they might engage in PTG. Results Fifty-four students completed the survey, which showed that PTG was uncommon. Attitudes were varied and context dependent. Most participants saw problems with PTG and favoured more explicit guidance on the issue. SNS usage was high ; participants were concerned by the content of their SNS profiles and who they were connecting with online. Participants showing high SNS use were 1.83 times more likely to have conducted PTG than lower use groups. Conclusions The diverse attitudes uncovered in this study indicated that teaching or guidelines could be useful to healthcare professionals considering PTG. Though ethically problematic, PTG may be important to patient care and safety. The decision to conduct PTG should be made with consideration of ethical principles and the intended use of the information. (shrink)

‘위인’ 정약용이 아닌 ‘인간’ 정약용을 찾아서... 한국 사상가들의 발자취를 찾아가는 ‘우리 인물 답사기’의 첫 책! 동녘 ‘우리 인물 답사기’ 시리즈의 첫 책. 이 시리즈는 철학 소설 형식으로 한국 사상가들의 삶과 사상을 들려준다. ‘달중과 미영’이라는 한국학을 공부하는 대학원생이 여러 인물들을 만나면서 그들과 대화를 하며 한국 사상가들을 인상적으로 스케치한다. 이 시리즈는 그동안 ‘위인’으로 바라보았던 사상가들의 얼굴을 한 겹 벗겨내고, 한 ‘인간’으로서의 모습을 그려내는 데 주력한다. 첫 번째로 찾아가는 인물은 18세기 실학사상을 집대성한 한국 최고의 학자이자 개혁가라고 평가받는 다산 정약용이다. 정약용에 관한 책은 많지만, (...) 평소 어렵고 두꺼운 인문서를 통해 정약용을 알아가는 데 아쉬움이 컸던 독자들에게 소설적 이야기로 풀어나가는 이 책은 흥미롭게 정약용의 삶에 접근하는 지름길이 되어준다. 먼저 등장하는 고교생 서연은 엄마를 아홉 살에 잃었다. 우연히 정약용도 아홉 살에 어머니를 여읜 사실을 알고 서연은 묘한 동질감을 느낀다. 어느 날 건축 일을 하는 아빠가 춘천 현장에서 한자로 ‘열수’라고 새겨진 모형 배를 줍게 되고, ‘열수’가 잘 알려지지 않은 정약용의 호라는 것을 알고 있던 서연은 그 배가 정약용과 관련이 있을 것이라고 생각한다. 아빠와 함께 남양주로 정약용 답사를 떠나기로 한 서연과 아빠는 정약용의 고향 ‘마재’에서 뜻밖의 귀인을 만나 함께 동행하게 되는데...... 마재, 여유당, 운길산 수종사, 수원 화성, 다산 초당, 강진 사의재... 정약용의 흔적이 묻어 있는 공간에서 그의 삶을 철학 소설로 풀다! (shrink)

Book synopsis: Background In 1998 Routledge published the Routledge Encyclopedia of Philosophy to critical acclaim. The first multi-volume Encyclopedia to be published in the discipline in over thirty years, REP is now regarded as the definitive resource in the field. Featuring 2,000 original entries from a team of over 1,300 of the world's most respected scholars and philosophers, REP swiftly accumulated rave reviews and awards, including selection by Library Journal as one of its 50 Sources for the Millenium, and recognition (...) as an Outstanding Reference Source by the American Library Association. Not content with resting on their laurels, the Routledge Encyclopedia of Philosophy editorial team, led by Professor Edward Craig, then began work on a fully searchable and extensively cross-referenced dynamic Web version, the Routledge Encyclopedia of Philosophy Online. REP Online expands this acclaimed Encyclopedia well beyond print reference boundaries. The full content of the classic 10-volume set remains at its core, but REP Online is also a living, growing resource designed to grow along with the discipline itself. Taking full advantage of the flexibility of the Web format, each year the REP editorial team brings a diverse range of new material, including newly commissioned entries by leading scholars, making REP Online the essential philosophy reference for faculty and students in a wide range of disciplines. As well as regular additions of new articles, REP Online also provides editorially reviewed links to other sites and resources on the web, revisions and updates of key entries, and periodic upgrades of the user environment. In keeping with the 1998 print set's tradition of first class editorial work and unparalleled breadth of subject matter, all new and revised entries are carefully integrated into the REP style and format and are connected to earlier material by the same kind and level of cross-referencing. Key Features · Covers an unparalleled breadth of subject matter, including Anglo-American, ethical and political, cross-cultural, interdisciplinary, continental and contemporary philosophy · Over 25,000 hot-linked cross-references between articles and new links to other editorially reviewed websites · An invaluable resource for all levels of users - students and general readers gain a rapid orientation with accessible summaries at the beginning of every in-depth article. There are 30 overview (signpost) articles which map their subject areas · Regularly upgraded with new material, revisions, and bibliographic updates, REP provides access to the latest scholarship and major developments in philosphical inquiry worldwide. (shrink)

Physicists regularly invoke universal laws, such as those of motion and electromagnetism, to explain events. Biological and medical scientists have no such laws. How then do they acquire a reliable body of knowledge about biological organisms and human disease? One way is by repeatedly returning to, manipulating, observing, interpreting, and reinterpreting certain subjects—such as flies, mice, worms, or microbes—or, as they are known in biology, “model systems.” Across the natural and social sciences, other disciplinary fields have developed canonical examples that (...) have played a role comparable to that of biology’s model systems, serving not only as points of reference and illustrations of general principles or values but also as sites of continued investigation and reinterpretation. The essays in this collection assess the scope and function of model objects in domains as diverse as biology, geology, and history, attending to differences between fields as well as to epistemological commonalities. Contributors examine the role of the fruit fly Drosophila and nematode worms in biology, troops of baboons in primatology, box and digital simulations of the movement of the earth’s crust in geology, and meteorological models in climatology. They analyze the intensive study of the prisoner’s dilemma in game theory, ritual in anthropology, the individual case in psychoanalytic research, and Athenian democracy in political theory. The contributors illuminate the processes through which particular organisms, cases, materials, or narratives become foundational to their fields, and they examine how these foundational exemplars—from the fruit fly to Freud’s Dora—shape the knowledge produced within their disciplines. Contributors Rachel A. Ankeny Angela N. H. Creager Amy Dahan Dalmedico John Forrester Clifford Geertz Carlo Ginzburg E. Jane Albert Hubbard Elizabeth Lunbeck Mary S. Morgan Josiah Ober Naomi Oreskes Susan Sperling Marcel Weber M. Norton Wise. (shrink)

Mental health challenges appear to be extremely problematic among correctional service employees, affecting persons working in community, institutional, and administrative correctional services. Focusing specifically on giving voice to correctional workers employed by the Ontario Ministry of Community Services and Corrections, we shed light on their interpretations of the complexities of their occupational work and of how their work affects staff. We show that participants encounter barriers to treatment seeking, which they describe as tremendous, starting with benefits, wages, and shift work. (...) We let the voices of staff elucidate what is needed to create a healthier correctional workforce. Recommendations include more training opportunities and programs; quarterly, semi-annual, or annual appointments with a mental health professional who can assess changes in the mental health status of employees; off-site assessments to ensure confidentiality; and team building opportunities to reduce inter-personal conflict at work and increase moral by improving the work environment. (shrink)

In an 1881 letter, Nietzsche remarks incredulously that he is "utterly amazed" to have found in Spinoza "a precursor" with whom he shares an "overtendency [...] to make knowledge the most powerful affect."1 It is this tendency to assign knowledge and ways of knowing the functional role of an affect that I intend to investigate as a means of overcoming affective nihilism.2 In particular, it is by participating in certain practices of self-knowledge and introducing oneself, experimentally, to new sites and (...) bodies of knowledge that one might reengage oneself with one's world and affirm life.In his work, Nietzsche describes affects as "reactions of the will", as "inclinations" and "aversions... (shrink)

This paper looks at various ways teleworking can be linked to surveillance in employment, making recommendations about how telework can be made more acceptable. Technological methods can allow managers to monitor the actions of teleworkers as closely as they could monitor "on site" workers, and in more detail than the same managers could traditionally. Such technological methods of surveillance or monitoring have been associated with low employee morale. For an employer to ensure health and safety may require inspections of (...) the teleworkplace. When the teleworkplace is in the home, there may be an invasion of privacy associated with such inspections, that could be perceived and resented as surveillance. A problem of telework is that teleworkers may feel isolated. Methods to counter this could be associated with further forms of surveillance, and fear of such surveillance may inhibit them from reaching their potential as methods to counter isolation. The idea that teleworking may also allow communications to be intercepted by third parties is also looked at. Some, but not all, of the issues considered are applicable, to some extent, in non-teleworked employment situations. The overall conclusion of the paper is that the potential exists for surveillance to be associated with telework. Fears of such surveillance may turn actors against telework. However, much can be done to reduce such fears. (shrink)

At times, the academy seems devoid of justice because it emphasizes the cultivation of knowledge often denied to marginalized individuals and communities. As black queer feminist scholars doing praxis-driven theorizing from separate fields on the subject of black queer families and communities, we employ research methods that resist the dynamics of power and privilege that exist within normative researcher-participant exchanges. In this essay, we explore and highlight the ethical, justice-oriented, and dialogical relationship between researcher-scholars and research participants. Through story and (...) theory, we illustrate and argue that autoethnographies and narrative interviews can act as epistemological excavation tools for both researchers and participants, as they become sites of individual and collective consciousness. Our work resists capitalist models of research and instead promotes a justice-oriented and community-derived building of knowledge. (shrink)

This article examines the way in which selfhood is constructed in direct-to-consumer advertisements for antidepressant medications. The sample consists of advertisements that appeared in nine popular magazines between 1997 and 2005, television commercials that ran between 2003 and 2005, and online promotional Web sites. The analysis is divided into three sections. First, it is argued that the ads rely on metaphors of communication, information exchange, and plenitude to construct a relationship between biology and selfhood. Second, in offering the choice for (...) antidepressant treatment, the ads grant individuals a new capacity for the exercise of personal agency. Third, the author describes antidepressants as pills that perform a narrative “magic.” In contrast to religious and psychoanalytic narratives that required individuals to incorporate disavowed elements of their selves into an ongoing life narrative, antidepressants are medications that allow individuals to put aside, or jump over, inexplicable and painful moments in their life. (shrink)

A term with myriad associations, revolution is commonly understood in its intellectual, historical, and sociopolitical contexts. Until now, almost no attention has been paid to revolution and questions of geography. Geography and Revolution examines the ways that place and space matter in a variety of revolutionary situations. David N. Livingstone and Charles W. J. Withers assemble a set of essays that are themselves revolutionary in uncovering not only the geography of revolutions but the role of geography in revolutions. Here, scientific (...) revolutions—Copernican, Newtonian, and Darwinian—ordinarily thought of as placeless, are revealed to be rooted in specific sites and spaces. Technical revolutions—the advent of print, time-keeping, and photography—emerge as inventions that transformed the world's order without homogenizing it. Political revolutions—in France, England, Germany, and the United States—are notable for their debates on the nature of political institutions and national identity. Gathering insight from geographers, historians, and historians of science, Geography and Revolution is an invitation to take the where as seriously as the who and the when in examining the nature, shape, and location of revolutions. (shrink)

A set of amino acid side chains that confer specificity for the coenzyme NADPH and the substrate glutathione in the flavoprotein disulphide oxidoreductase, glutathione reductase, has been identified. Systematic replacement of these amino acid residues in the coenzyme‐binding site switches the specificity of the enzyme from its natural strong preference for NADPH to a marked preference For NADH. The amino acids replaced all lie in a structural motif within the dinucleotide‐binding domain of the protein. Since this domain is a (...) feature common to most dehydrogenases (reductases) that use nicotinamide coenzymes, it may be that the coenzyme specificities of all such enzymes can be manipulated in this way. Similarly, amino acid residues involved in the selective recognition of trypanothione by trypanothione reductase, an enzyme related to glutathione reductase and exclusive to trypanosomatids, were identified. Suitable mutation of the corresponding residues in E. coli glutathione reductase switched its substrate specificity towards trypanothione. A better understanding of the substrate specificity of these enzymes could open up a route to the chemotherapy of trypanosomal infections. (shrink)

A landslide inventory is a detailed register of the spatial distribution, geometry, and attributes of landslides and is essential for landslide hazard analysis, risk management, regional planning, and land use management and development, especially in landslide-prone regions. However, the development of a national landslide inventory is time-consuming and costly. Accordingly, most developing countries, including Sri Lanka, have basic landslide databases, which identify the location, date, and time of occurrence on a point map. This study, therefore, aimed to introduce a new (...) method to report landslide information via a mobile application based on a participatory approach with information recorded in a web portal called the participatory landslide inventory. Twenty-one landslide site locations and their attributes were captured on the PLI web portal using the PLI mobile app. The system administrator then demarcated the landslide boundaries and performed geometrical calculations for each landslide to complete the inventory. Finally, the landslide information was published through the PLI web portal. The PLI is an effective and efficient tool for developing a landslide inventory economically. (shrink)

Increasing interest in farmers’ local soil knowledge and soil management practice as a way to promote sustainable agriculture and soil conservation needs a reliable means to connect to it. This study sought to examine if Visual Soil Assessment and farmer workshops were suitable means to engage, communicate and preserve farmers’ LSK in two mountainous communes of Central Vietnam. Twenty-four farmers with reasonable or comprehensive LSK from previously studied communes were selected for the efficacy of VSA and farmer workshops for integrating (...) LSK into a well-accepted soil assessment tool. In field sites chosen by the farmers, VSA was independently executed by both farmers and scientists at the same time. Close congruence of VSA scores between the two groups highlighted that farmers could competently undertake VSA. Farmers’ VSA score was compared with their perception of field’s soil quality. For the majority of farmers’ perception of soil quality was consistent to their VSA score, while the remainder perceived their soil quality was lower than their VSA score. For most farmers their assessment of soil quality using VSA valued their LSK, and the two measures were well aligned. Soil colour and presence or vulnerability to erosion were common soil characteristics mentioned by farmers and affected the final VSA score. Farmers’ participation in VSA and workshops strengthen farmers’ confidence in their LSK and provided guidance on the impact of their soil management on soil improvement and conservation. (shrink)

The phrase ‘the edge of race’ can be used both as a description and as a response to two key concerns. The first of these is that while race is increasingly on the periphery of education policy – with a growing disregard shown for racist inequities, as education systems become dominated by market-driven concerns – it is important that we map the shifting relations of race in neoliberal politics and policies. The second concern is that at this time, within and (...) outside the spaces of the academy, even to mention race equity is to risk condemnation, marginalization, and ridicule. The authors in this collection use ‘the edge of race’ as a provocation in order to examine the concepts, methodologies, policies, politics, processes, and practices associated with race and racism in education. The chapters offer empirical examples of the perpetuation and perniciousness of racism that point to the continued salience of research about race. Additionally, the chapters make contributions to conceptual and methodological understandings of race and racism. The contributors illustrate the contingency, productivity, and fragility of race as a concept, and point to how educational research continues to be a contested site in, and from which to study, race and education. This book was originally published as a special issue of _Discourse: Studies in the Cultural Politics of Education. _. (shrink)

In this note, I plan to describe some of the procedures I followed in creating the World Wide Web site for the Metaphysics Research Lab at CSLI. Its URL (Uniform Resource Locator) is.

Recent studies on colonial discourse have demonstrated that the speeches of freedom activists in colonial Africa served as sites of resistance. One key text type that has, however, been neglected in the critical literature on the discourse of emancipation is the national anthem of colonised states. To fill this gap, the present study examines the discursive enactment of resistance in the anthems of former British colonies in Africa, focusing on the transitivity framework in systemic functional linguistics. Semantic and structural parallelisms (...) across the anthems are identified as evidence of a collective memory, a cultural trauma reconfigured and reconstituted to reclaim a positive identity and project a desirable postcolonial future. They also foreground the motif of freedom and legitimise the African as the owner of the reclaimed territory. These procedures articulate an anti-imperialist and anti-establishment stance that provides hope, strength and encouragement to an oppressed group. This paper extends the scholarship on the discursive enactment of resistance by focusing attention on a context underexplored in the literature. It also illustrates the (re)construction of relevant ideologies in national anthems to stimulate desirable, progressive attitudes among citizenry in African states. The paper is furthermore significant to decolonial research and highlights the role of language in political decolonisation processes. (shrink)

Farm to institution (FTI) efforts aim to increase the amount of locally produced foods, typically fruits and vegetables, served by institutions such as schools, colleges, hospitals, senior meal sites, and correctional facilities. Scholars have cited these efforts as contributing to public health and community-based food systems goals. Prior research has found that relationships based on shared values have played a critical role in motivating and sustaining FTI efforts. We review previous studies, discussing values that motivate participation, and affect practices and (...) relationships in FTI supply chains. We use semi-structured interviews to better understand supply chain actors’ values and motivations and how they affect behaviors, with the aim of informing efforts to increase the scope and effectiveness of FTI efforts. All participants are currently engaged in FTI efforts. We find a mix of social and economic values were present for farmers, distributors, and buyers. Our implications focus on the importance of shared values and relationships, the benefit of local food for businesses along the supply chain, and the potential of non-school institution markets as entry points for farmers. (shrink)

We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate (...) assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

The SSIS SEL Brief Scales are multi-informant measures that were developed to efficiently assess the SEL competencies of school-age youth in the United States. Recently, the SSIS SELb was translated into multiple languages for use in a multi-site study across six European countries. The purpose of the current study was to examine concurrent and predictive evidence for the SEL Composite scores from the translated versions of the SSIS SELb Scales. Results indicated that SSIS SELb Composite scores demonstrated expected positive (...) concurrent and predictive relationships with scores from the Connor-Davidson Resilience Scale and negative relationships with scores from the problem behavior scales of the Strengths and Difficulties Questionnaire. Although there were a few exceptions, these patterns generally were consistent across informants and samples providing initial validity evidence for the Composite score from the translated versions of the SSIS SELb Scales. Limitations and future research directions are discussed. (shrink)

Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 (...) was suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (shrink)

Background The use of lengthy, detailed, and complex informed consent forms is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in (...) biomedical research. Methods This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 to 5. Results Of the 2484 questionnaires distributed, 2113 were returned. The majority of respondents considered most elements required in the ICF to be ‘moderately important’ to ‘very important’ for their decision making. Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF. Conclusions Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF. (shrink)

Increasing ethical attention and debate is focusing on whether individuals who take part in clinical trials should be given access to post-trial care. However, the main focus of this debate has been upon drug trials undertaken in low-income settings. To broaden this debate, we report findings from interviews with individuals (n = 24) who participated in a clinical trial of a closed-loop system, which is a medical device under development for people with type 1 diabetes that automatically adjusts blood glucose (...) to help keep it within clinically recommended ranges. Individuals were recruited from UK sites and interviewed following trial close-out, at which point the closed-loop had been withdrawn. While individuals were stoical and accepting of the requirement to return the closed-loop, they also conveyed varying degrees of distress. Many described having relaxed diabetes management practices while using the closed-loop and having become deskilled as a consequence, which made reverting back to pre-trial regimens challenging. Participants also described unanticipated consequences arising from using a closed-loop. As well as deskilling, these included experiencing psychological and emotional benefits that could not be sustained after the closed-loop had been withdrawn and participants reevaluating their pre- and post-trial life in light of having used a closed-loop and now perceiving this life much more negatively. Participants also voiced frustrations about experiencing better blood glucose control using a closed-loop and then having to revert to using what they now saw as antiquated and imprecise self-management tools. We use these findings to argue that ethical debates about post-trial provisioning need to be broadened to consider potential psychological and emotional harms, and not just clinical harms, that may result from withdrawal of investigated treatments. We also suggest that individuals may benefit from information about potential nonclinical harms to help make informed decisions about trial participation. (shrink)

Attempts to solve the puzzling problem of oxidative phosphorylation led to four very different hypotheses each of which suggested a different view of the ATP synthase, the phosphorylating enzyme. During the 1960s and 1970s evidence began to accumulate which rendered Peter Mitchell’s chemiosmotic hypothesis, the novel part of which was the proton translocating ATP synthase (ATPase), a plausible explanation. The conformational hypothesis of Paul Boyer implied an enzyme where ATP synthesis was driven by the energy of conformational changes in the (...) respiratory proteins. This was finally abandoned as an explanation of the overall process. Nevertheless the conformational understanding of the enzyme became an acceptable proposal during the early 1970s and eventually led Boyer to a view of the enzyme that incorporated both hypotheses. The correspondence between Mitchell and Boyer, both Nobel laureates, exposes their different approaches to both this enzyme and to the hypotheses of oxidative phosphorylation and illuminates a key step in the development of bioenergetics. In particular Boyer was suspicious of proton gradients, because he could not envisage a chemical mechanism for the synthesis of ATP, while Mitchell distrusted conformational arguments because he believed the proton must act vectorially at the active site of the enzyme. This resulted in two different views of the mechanisms operating in this enzyme. Ultimately while Boyer was able to marry the two approaches, Mitchell retained his insistence on the role of the proton at the active site and was thus unable to give significance to Boyer’s conformational ideas. The underlying issues in this debate are discussed particularly with reference to the differing styles of Boyer and Mitchell and the influence of molecular biology, especially the development of protein technology. (shrink)

While the critically oriented writings of Immanuel Kant remain the key theoretical grounds from which universalists challenge reduction of international rights law and protection to the practical particularities of sovereign states, Kant’s theory can be read as also a crucial argument for a human rights regime ordered around sovereign states and citizens. Consequently, universalists may be tempted to push Kant’s thinking to greater critical examination of ‘the human’ and its properties. However, such a move to more theoretical rigour in critique (...) only solidifies the subversive statism of Kant’s apparent universalism, as long as it remains embedded in his prior theory of critical philosophy that privileges a singular form of reason. Universalist theories of human rights can break with this contradiction only insofar as they also displace the right to philosophy from the subject and site of ‘civil’ man to a politics of theory where no such subject or site is guaranteed. (shrink)

In many experimental sciences, like particle physics or molecular biology, the proper place for establishing facts is the laboratory. In the sciences of population biology, however, the laboratory is often seen as a poor approximation of what occurs in nature. Results obtained in the field are usually more convincing. This raises special problems: it is much more difficult to obtain stable, repeatable results in the field, where environmental conditions vary out of the experimenter’s control, than in the laboratory. We examine (...) here how this problem affected an influential experimental research tradition in community ecology, the study of the ecology of the rocky seashores. In the 1960s, a handful of North-American ecologists, most notably Joseph Connell, Robert Paine and Paul Dayton, made the rocky seashores a model study system for experimenting in the field. Their experiments were deceptively simple: they removed species living on the seashore and described the resulting effects on the local ecology. These experiments exerted a deep influence on community ecology. They provided evidence for speculative developments concerning the theory of interspecific competition, the factors responsible for species richness and the ecology of food webs. They also stimulated novel conceptual developments. In particular, Paine developed the predation hypothesis, which states that the presence of predators can favour species richness, before introducing the keystone species concept, according to which some species exert disproportionate effects on ecological systems. More broadly, these experiments gave support to a methodological trend in favour of field experimentation. Only controlled perturbations in the field, it seemed, provided a reliable method to get insights into the structure of ecological communities. However, as experiments were continued in time and repeated in different sites, divergent results appeared. We analyse here how intertidal researchers coped with the variability of environmental conditions and tried to stabilize their results. In the process, they reconsidered not only their early conclusions, but also the exclusive status given to field experiments. Expanding on this case study, we discuss some significant differences between laboratory and field experiments. (shrink)

Photonic Crystals is the first book to address one of the newest and most exciting developments in physics--the discovery of photonic band-gap materials and their use in controlling the propagation of light. Recent discoveries show that many of the properties of an electron in a semiconductor crystal can apply to a particle of light in a photonic crystal. This has vast implications for physicists, materials scientists, and electrical engineers and suggests such possible developments as an entirely optical computer. Combining cutting-edge (...) research with the basic theoretical concepts behind photonic crystals, the authors present to undergraduates and researchers a concise, readable, and comprehensive text on these novel materials and their applications. The first chapters develop the theoretical tools of photonic crystals in a broad, intuitive fashion, starting from nothing more than Maxwell's equations and Fourier analysis, and include analogies to traditional solid-state physics and quantum theory. There follows an investigation of the unique phenomena that take place within photonic crystals, at defect sites, and at surfaces and interfaces. The authors offer a new treatment of the traditional multilayer film (a one-dimensional photonic crystal), which allows for the extension to higher dimensions and more complex geometries. After exploring the capabilities of photonic crystals to guide and localize light, the authors demonstrate how these notions can be put to work. (shrink)

This article draws on the conceptualisation of ‘discursive formation’ to examine the particular configuration of the ‘objects, subjects, concepts and strategies’ which constituted ‘nuclear proliferation’ between 2006 and 2012. While previous studies have mostly explored the discourse of nuclear proliferation through the analysis of newspaper texts, few have considered corpora from different sites or considered the changes, transformations and contradictions that take place when meanings are delocated from one site and relocated in another. Elements of poststructuralist discourse theory, critical (...) linguistics and corpus linguistics are brought together to consider how events were constructed within two corpora: UN Security Council resolutions and newspaper articles published in prominent UK and US broadsheets. WordSmith Tools was used to analyse word frequencies, statistical patterns of keywords, word collocation profiles and concordance patterns. Results indicate that the most salient lexical items refer to actors, strategic actions and technologies. As these constituents of nuclear proliferation are delocated from the political sphere and relocated in the public sphere, three discursive strategies unfold: personalisation, normalisation or exceptionalisation, and reification. (shrink)

Organismal form arises by the coordinated movement, arrangement, and activity of cells. In metazoans, most morphogenetic programs that establish the recognizable body plan of any given species are initiated during the developmental period, although in many species growth continues throughout life. By comparing the cellular and molecular development of the bilaterians (bilaterally symmetrical animals) to the development of their closest outgroup, the cnidarians, it appears that morphogenesis and the cell fate specification associated with germ layer formation during the process of (...) gastrulation are separately controlled by two distinct downstream pathways (canonical and planar cell polarity) of Wnt signaling. Furthermore, a fundamental change in the early developmental program, the positioning of the site of gastrulation, allowed the spatial separation of gene regulatory networks that facilitated the rapid diversification of bilaterian body plans. (shrink)

Major hallmarks of Alzheimer's disease include brain deposition of the amyloid-beta peptide , which is proteolytically cleaved from a large Abeta precursor protein by beta and gamma- secretases. A transmembrane aspartyl protease, beta-APP cleaving enzyme , has been recognized as the beta-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5'-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region and 5'-untranslated (...) region contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the "ATG" start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD. (shrink)