Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

The Aristotelian dictum that desire is the starting point of practical reasoning that ends in action can of course be denied. Its denial is a commonplace of moral theory in the tradition of Kant. But in this essay I am concerned with that issue only indirectly. I shall not contend that rational action always or necessarily does involve desire as its starting point; nor shall I deny it. My question concerns instead the possibility of its ever beginning in desire. For (...) there is a question whether it is even possible for reasoning to begin in desire, a question arising from the nature of desire and its objects, which to my knowledge has not been articulated. If we can see how desire can provide the arche of action, then we can consider later, and from that vantage point, whether it is necessary that it should do so. It will, I think, be possible eventually to argue that if practical reasoning has the character it must have, if it can begin in desire, then its starting point can be nothing but desire. (shrink)

Offers a physical explanation of the Coriolis force. This book is useful for studying the hydrodynamics of the ocean and atmosphere. It also presents many aspects of classical mechanics/dynamics physics. It explains the complexities of this force, about which many scientists have had lingering uncertainties since it was first described in 1831.

Bio-ontologies are essential tools for accessing and analyzing the rapidly growing pool of plant genomic and phenomic data. Ontologies provide structured vocabularies to support consistent aggregation of data and a semantic framework for automated analyses and reasoning. They are a key component of the Semantic Web. This paper provides background on what bio-ontologies are, why they are relevant to botany, and the principles of ontology development. It includes an overview of ontologies and related resources that are relevant to plant science, (...) with a detailed description of the Plant Ontology (PO). We discuss the challenges of building an ontology that covers all green plants (Viridiplantae). Key results: Ontologies can advance plant science in four keys areas: 1. comparative genetics, genomics, phenomics, and development, 2. taxonomy and systematics, 3. semantic applications and 4. education. Conclusions: Bio-ontologies offer a flexible framework for comparative plant biology, based on common botanical understanding. As genomic and phenomic data become available for more species, we anticipate that the annotation of data with ontology terms will become less centralized, while at the same time, the need for cross-species queries will become more common, causing more researchers in plant science to turn to ontologies. (shrink)

The Plant Ontology (PO; http://www.plantontology.org/) is a publicly-available, collaborative effort to develop and maintain a controlled, structured vocabulary (“ontology”) of terms to describe plant anatomy, morphology and the stages of plant development. The goals of the PO are to link (annotate) gene expression and phenotype data to plant structures and stages of plant development, using the data model adopted by the Gene Ontology. From its original design covering only rice, maize and Arabidopsis, the scope of the PO has been expanded (...) to include all green plants. The PO was the first multi-species anatomy ontology developed for the annotation of genes and phenotypes. Also, to our knowledge, it was one of the first biological ontologies that provides translations (via synonyms) in non-English languages such as Japanese and Spanish. There are about 2.2 million annotations linking PO terms to over 110,000 unique data objects representing genes or gene models, proteins, RNAs, germplasm and Quantitative Traits Loci (QTLs) from 22 plant species. In this paper, we focus on the plant anatomical entity branch of the PO, describing the organizing principles, resources available to users, and examples of how the PO is integrated into other plant genomics databases and web portals. We also provide two examples of comparative analyses, demonstrating how the ontology structure and PO-annotated data can be used to discover the patterns of expression of the LEAFY (LFY) and terpene synthase (TPS) gene homologs. (shrink)

Plants from a handful of species provide the primary source of food for all people, yet this source is vulnerable to multiple stressors, such as disease, drought, and nutrient deficiency. With rapid population growth and climate uncertainty, the need to produce crops that can tolerate or resist plant stressors is more crucial than ever. Traditional plant breeding methods may not be sufficient to overcome this challenge, and methods such as highOthroughput sequencing and automated scoring of phenotypes can provide significant new (...) insights. Ontologies are essential tools for accessing and analysing the large quantities of data that come with these newer methods. As part of a larger project to develop ontologies that describe plant phenotypes and stresses, we are developing a plant disease extension of the Infectious Disease Ontology (IDOPlant). The IDOPlant is envisioned as a reference ontology designed to cover any plant infectious disease. In addition to novel terms for infectious diseases, IDOPlant includes terms imported from other ontologies that describe plants, pathogens, and vectors, the geographic location and ecology of diseases and hosts, and molecular functions and interactions of hosts and pathogens. To encompass this range of data, we are suggesting inOhouse ontology development complemented with reuse of terms from orthogonal ontologies developed as part of the Open Biomedical Ontologies (OBO) Foundry. The study of plant diseases provides an example of how an ontological framework can be used to model complex biological phenomena such as plant disease, and how plant infectious diseases differ from, and are similar to, infectious diseases in other organism. (shrink)

The Plant Ontology (PO) (http://www.plantontology.org) (Jaiswal et al., 2005; Avraham et al., 2008) was designed to facilitate cross-database querying and to foster consistent use of plant-specific terminology in annotation. As new data are generated from the ever-expanding list of plant genome projects, the need for a consistent, cross-taxon vocabulary has grown. To meet this need, the PO is being expanded to represent all plants. This is the first ontology designed to encompass anatomical structures as well as growth and developmental stages (...) across such a broad taxonomic range. While other ontologies such as the Gene Ontology (GO) (The Gene Ontology Consortium, 2010) or Cell Type Ontology (CL) (Bard et al., 2005) cover all living organisms, they are confined to structures at the cellular level and below. The diversity of growth forms and life histories within plants presents a challenge, but also provides unique opportunities to study developmental and evolutionary homology across organisms. (shrink)

The Planteome project provides a suite of reference and species-specific ontologies for plants and annotations to genes and phenotypes. Ontologies serve as common standards for semantic integration of a large and growing corpus of plant genomics, phenomics and genetics data. The reference ontologies include the Plant Ontology, Plant Trait Ontology, and the Plant Experimental Conditions Ontology developed by the Planteome project, along with the Gene Ontology, Chemical Entities of Biological Interest, Phenotype and Attribute Ontology, and others. The project also provides (...) access to species-specific Crop Ontologies developed by various plant breeding and research communities from around the world. We provide integrated data on plant traits, phenotypes, and gene function and expression from 95 plant taxa, annotated with reference ontology terms. (shrink)

Students in 80 kindergarten to grade six classrooms photographed and captioned experiences in class which they identified as examples of democratic citizenship education. With the assistance of a teacher candidate placed in their classroom for a semester, students chose and captioned five of the photographs they considered to best represent demonstrate citizenship education. Four main categories of citizenship events emerged describing key elements associated with democratic citizenship education; shared decision making, participating in a learner-oriented classroom context in which students have (...) some individual choice of daily activities, equality of opportunity, and activities extending into the community and integrating community and classroom. Early grades students (K-3) identified activities they associated with democratic citizenship education while upper grades (4-6) students additionally presented rationales and gave evidence to support their representations. Empowerment, problem solving, and contributing to the common good were additional elements associated with democratic citizenship education in the classes sampled, although these were not strongly represented as were the four key elements. This study provides an initial portrait indicating a need for deeper investigation of K-6 students' own representations of the democratic citizenship education they experience. (shrink)

Students in 80 kindergarten to grade six classrooms photographed and captioned experiences in class which they identified as examples of democratic citizenship education. With the assistance of a teacher candidate placed in their classroom for a semester, students chose and captioned five of the photographs they considered to best represent demonstrate citizenship education. Four main categories of citizenship events emerged describing key elements associated with democratic citizenship education; shared decision making, participating in a learner-oriented classroom context in which students have (...) some individual choice of daily activities, equality of opportunity, and activities extending into the community and integrating community and classroom. Early grades students identified activities they associated with democratic citizenship education while upper grades students additionally presented rationales and gave evidence to support their representations. Empowerment, problem solving, and contributing to the common good were additional elements associated with democratic citizenship education in the classes sampled, although these were not strongly represented as were the four key elements. This study provides an initial portrait indicating a need for deeper investigation of K-6 students' own representations of the democratic citizenship education they experience. (shrink)

This textbook offers a unique and accessible approach to ethical decision-making for practicing pharmacists and student pharmacists. Unlike other texts, it gives clear guidance based on the fundamental principles of moral philosophy, explaining them in simple language and illustrating them with abundant clinical examples and case studies. The strength of this text is in its emphasis on normative ethics and critical thinking, and that there is truly a best answer in the vast majority of cases, no matter how complex. The (...) authors place high trust in a pharmacist’s moral judgment. This teaches the reader how to think, based on ethical principles, not necessarily what to think. This means navigating between the two extremes of overly theoretical and excessively prescriptive. The cogent framework given in this text uses the language of competing duties, identifying the moral principles at stake that create duties for the pharmacist. This is the balancing act of normative ethics, and of deciding which duties should prevail in a given clinical situation. This work presents a clear-cut pathway for resolving ethical dilemmas encountered by pharmacists, based on foundational principles and critical thinking. Presents a clear-cut pathway for resolving the ethical dilemmas encountered by pharmacists, based on foundational principles and critical thinking. Jon E. Sprague, RPh, PhD, Director of Science and Research for the Ohio Attorney General. (shrink)

Achieving understanding of nature is one of the aims of science. In this paper we offer an analysis of the nature of scientific understanding that accords with actual scientific practice and accommodates the historical diversity of conceptions of understanding. Its core idea is a general criterion for the intelligibility of scientific theories that is essentially contextual: which theories conform to this criterion depends on contextual factors, and can change in the course of time. Our analysis provides a general account of (...) how understanding is provided by scientific explanations of diverse types. In this way, it reconciles conflicting views of explanatory understanding, such as the causal-mechanical and the unificationist conceptions. (shrink)

This paper examines the critical role that organizational leaders play in establishing a values based climate. We discuss seven mechanisms by which leaders convey the importance of ethical values to members, and establish the expectations regarding ethical conduct that become engrained in the organizations climate. We also suggest that leaders at different organizational levels rely on different mechanisms to transmit values and expectations. These mechanisms then influence members practices and expectations, further increase the salience of ethical values and result in (...) the shared perceptions that form the organizations climate. The paper is organized in three parts. Part onebegins with a brief discussion of climates regarding ethics and the critical role of values. Part two provides discussion on the mechanisms by which leaders and members transmit values and create climates related to ethics. Part three provides a discussion of these concepts with implications for theory, research, and practice. (shrink)

This study proposes a conceptual model to explain persistent, accepted-as-normal corporate wrongdoing (hereafter banality of wrongdoing), particularly for high performance organizations. The model describes five explanatory variables: the culture of competition, ends-biased leadership, missionary zeal, legitimizing myth, and the corporate cocoon. Our thesis is that the nature of competition drives both legitimate and illegitimate goal-seeking to adopt an iconoclastic (rule-breaking) orientation. High performance organizations are favorable hosts for wrongdoing because high performance requires aggressive behavior at the ethical margins of what (...) is acceptable. The way leadership reacts to competition sets the stage for ethical or unethical cultures to develop. Ends-biased leadership will project strong vision, using ideology and legitimizing myth as tools to inspire and motivate. The resulting missionary zeal justifies using questionable means because of the perceived value of the end. One critical method for building strong culture is creating a sense of being separate and apart from the ordinary. This cocoon effect may create a self-referential value system that is significantly at odds with mainstream culture and in which wrongdoing is banal. We intend an empirical study of the variables described in this model. (shrink)

Models of the EPR-Bohm experiment usually consider just two times, an initial time, and the time of measurement. Within such analyses, it has been argued that locality is equivalent to determinism, given the strict correlations of quantum mechanics. However, an analysis based on such models is only a preliminary to an analysis based on a complete dynamical model. The latter analysis is carried out, and it is shown that, given certain definitions of locality and determinism for completely dynamical models, locality (...) implies, but is not implied by, determinism. Further, it is suggested that a local deterministic model has not been ruled out by Bell's theorem. It is suggested that such a model could naturally deny the independence of initial complete states from the settings of the apparatuses (a crucial assumption in the derivation of Bell's inequality). (shrink)