In the mouse, at least 16 genes regulate vesicle trafficking to specialized lysosome‐related organelles, including platelet dense granules and melanosomes. Fourteen of these genes have been identified by positional cloning. All 16 mouse mutants are models for the genetically heterogeneous human disease, Hermansky–Pudlak Syndrome (HPS). Five HPS genes encode known vesicle trafficking proteins. Nine genes are novel, are found only in higher eukaryotes and encode members of three protein complexes termed BLOCs (Biogenesis of Lysosome‐related Organelles Complexes). Mutations in murine HPS (...) genes, which encode protein co‐members of BLOCs, produce essentially identical phenotypes. In addition to their well‐known effects on pigmentation, platelet function and lysosome secretion, HPS genes control a wide range of physiological processes including immune recognition, neuronal functions and lung surfactant trafficking. Studies of the molecular functions of HPS proteins will reveal important details of vesicle trafficking and may lead to therapies for HPS. BioEssays 26:616–628, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The picture-word interference paradigm has been used to investigate the time course of processes involved in word retrieval, but is challenging to implement online due to dependence on measurements of vocal reaction time. We performed a series of four experiments to examine picture-word interference and facilitation effects in a form of covert picture naming, with and without gamification. A target picture was accompanied by an audio word distractor that was either unrelated, phonologically-related, associatively-related, or categorically-related to the picture. Participants were (...) instructed to judge whether the name of the target picture ended in the phoneme assigned to the block by pressing corresponding keys as quickly and accurately as possible. Experiments 1 and 2 successfully replicated categorical interference and phonological facilitation effects at different optimal stimulus-onset-asynchronies between words and pictures. Experiment 3 demonstrated that a key gamification feature motivated faster speed at the expense of accuracy in the gamified vs. experimental format of the task. Experiment 4 adopted the optimal SOAs and verified that the gamification reveals expected interference and facilitation effects despite the speed-accuracy tradeoff. These studies confirmed that categorical interference occurs earlier than phonological facilitation, while both processes are independent from articulation and inherent to word retrieval itself. The covert PWI paradigm and its gamification have methodological value for neuroimaging studies in which articulatory artifacts obscure word retrieval processes, and may be developed into potential online word-finding assessments that can reveal word retrieval difficulties with greater sensitivity. (shrink)

We give a survey of the study of nonstandard models in recursion theory and reverse mathematics. We discuss the key notions and techniques in effective computability in nonstandard models. and their applications to problems concerning combinatorial principles in subsystems of second order arithmetic. Particular attention is given to principles related to Ramsey's Theorem for Pairs.

We give a survey of the study of nonstandard models in recursion theory and reverse mathematics. We discuss the key notions and techniques in effective computability in nonstandard models, and their applications to problems concerning combinatorial principles in subsystems of second order arithmetic. Particular attention is given to principles related to Ramsey’s Theorem for Pairs.

This book provides practical and research-based chapters that offer greater clarity about the particular kinds of teacher reflection that matter and avoids talking about teacher reflection generically, which implies that all kinds of reflection are of equal value.

The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing the (...) 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

The target article argues researchers should be more ambitious, designing studies that systematically and comprehensively explore the space of possible experiments in one fell swoop. We argue that while “systematic” is rarely achievable, “comprehensive” is often enough. Critically, the recent popularization of massive online experiments shows that comprehensive studies are achievable for most cognitive and behavioral research questions.

This co-edited volume compares Chinese and Western experiences of engineering, technology, and development. In doing so, it builds a bridge between the East and West and advances a dialogue in the philosophy of engineering. Divided into three parts, the book starts with studies on epistemological and ontological issues, with a special focus on engineering design, creativity, management, feasibility, and sustainability. Part II considers relationships between the history and philosophy of engineering, and includes a general argument for the necessity of dialogue (...) between history and philosophy. It continues with a general introduction to traditional Chinese attitudes toward engineering and technology, and philosophical case studies of the Chinese steel industry, railroads, and cybernetics in the Soviet Union. Part III focuses on engineering, ethics, and society, with chapters on engineering education and practice in China and the West. The book’s analyses of the interactions of science, engineering, ethics, politics, and policy in different societal contexts are of special interest. The volume as a whole marks a new stage in the emergence of the philosophy of engineering as a new regionalization of philosophy. This carefully edited interdisciplinary volume grew out of an international conference on the philosophy of engineering hosted by the University of the Chinese Academy of Sciences in Beijing. It includes 30 contributions by leading philosophers, social scientists, and engineers from Australia, China, Europe, and the United States. (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)

In everyday life, assumptions about our peers' as well as our own personality shape social interactions. We investigated whether self-rated personality and inferences drawn from partners' faces influence economic decisions. Participants (N= 285) played the trust game in the role of the trustor as well as the ultimatum game in the role of the proposer and interacted with trustees and receivers represented by prototypical personality faces. Participants also evaluated both their own traits and the personality of the faces. In the (...) trust game, trustees represented by faces rated higher on agreeableness yielded higher transferred amounts. This effect was more pronounced for trustors low on dispositional trust, whereas trustors high on dispositional trust did not relate their decisions to the faces. Trustees represented by faces rated higher on conscientiousness yielded higher transferred amounts only for trustors high on dispositional anxiety. In the ultimatum game, receivers represented by faces rated higher on conscientiousness yielded lower offers only for proposers high on dispositional assertiveness. These results extend previous findings on the inferences drawn from facial features and the influence of personality on decision making. They highlight the importance of considering the personality of both interaction partner, as well as potential interactions of players' traits. (shrink)

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

It is a platitude that belief is subject to a standard of correctness: a belief is correct if and only if it is true. But not all standards of correctness are authoritative or binding. Some standards of correctness may be arbitrary, unjustified or outrightly wrong. Given this, one challenge to proponents of the truth norm of belief, is to answer what Korsgaard (1996) calls ‘the normative question’. Is the truth norm of belief authoritative or binding regarding what one ought to (...) or may believe? If so, what grounds its authority? The aim of this paper is to offer a novel answer to the grounding challenge on a reason-based normative framework. I develop and defend a practice-based account of the truth norm, according to which, the authority of the truth norm of belief is grounded in what I call the T-practice, a justified social practice that functions to facilitate knowledge production, maintenance, and social cooperation. (shrink)

Introduction While quizzing during informed consent for research to ensure understanding has become commonplace, it is unclear whether the quizzing itself is problematic for potential participants. In this study, we address this issue in a multinational HIV prevention research trial enrolling injection drug users in China and Thailand. Methods Enrolment procedures included an informed consent comprehension quiz. An informed consent survey followed. Results 525 participants completed the informed consent survey (Heng County, China=255, Xinjiang, China=229, Chiang Mai, Thailand=41). Mean age was (...) 33 and mean educational level was 8 yrs. While quizzing was felt to be a good way to determine if a person understands the nature of clinical trial participation (97%) and participants did not generally find the quiz to be problematic, minorities of respondents felt pressured (6%); anxious (5%); bored (5%); minded (5%); and did not find the questions easy (13%). In multivariate analysis, lower educational level was associated with not minding the quizzing (6–10 yrs vs 0–5 yrs: OR=0.27, p=0.03; more than 11 yrs vs 0–5 yrs: OR=0.18, p=0.03). There were also site differences (Heng County vs Xinjiang) in feeling anxious (OR=0.07; p=<0.01), not minding (OR=0.26; p=0.03), being bored (OR=0.25; p=0.01) and not finding the questions easy (OR=0.10; p=<0.01). Conclusions Quizzing during the informed consent process can be problematic for a minority of participants. These problems may be associated with the setting in which research takes place and educational level. Further research is needed to develop, test and implement alternative methods of ensuring comprehension of informed consent. Trial Registration clinicaltrials.gov number NCT00270257. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Journal of the History of Philosophy 41.3 (2003) 409-410 [Access article in PDF] Christoph Riedweg. Pythagoras: Leben, Lehre, Nachwirkung. Munich: Beck, 2002. Pp. 206. Cloth, € 19.90.Another book about Pythagoras? Hasn't it been shown that we do not have any precise information about him, especially about his contributions as a scholar and a philosopher? Maybe we have been overly skeptical about the information transmitted about Pythagoras. In Pythagoras: Leben, (...) Lehre, Nachwirkung, Christoph Riedweg suggests we should take a different perspective, and he shows what we might gain if we loosen our standards on what counts as information about Pythagoras's contribution to the history of philosophy and science. We can reconstruct a cluster of ideas, motifs, and motivations relevant for early Pythagoreanism. This will give us an idea of the factors influencing Pythagoras and those influenced in turn by him. Even if we will not know what exactly he claimed or achieved (whether he did or did not use the Pythagorean psephoi, for example), we can still get a reasonably informative (if somewhat fuzzy) picture of Pythagoras's contribution and his significance. Riedweg's book outlines the terrain for such an approach. It is what it announces to be: an introduction (Einführung). It does not promise, nor does it offer, any radically new theories on Pythagoras.I will focus on chapters 2 and 3 (61-149) of the book. After a survey of ancient reports and legends about Pythagoras (chapter 1), Riedweg approaches the historical Pythagoras through a sketch of the cultural setting in which he lived and worked, and through the reactions of his contemporaries and near contemporaries (chapter 2, sections 1-2). Unfortunately, a reference to the socio-political sphere is missing. This is a serious gap, given the poignancy of the socio-political changes in the sixth-century Ionian poleis, and given Pythagoras's cooperation with the local aristocratic elites, for political purposes. One is, however, provided with a sketch of the contemporary cultural setting in which Pythagoras put forth his religious and his philosophical teachings—philosophy, art, technology, contacts (chapter 2, section 1). Apparently (Riedweg documents this conclusively), Pythagoras provoked extreme reactions from the very beginning, even from people that lived far away. Riedweg's label "Charismatiker"—a borrowing from Weberian sociology of religion—seems fitting. The sixth- and fifth-century "outside" testimonies (chapter 2, section 2) are predominantly polemical. In the religious sphere, Pythagoras comes across as a mystic, with a guru-attitude. But he also constructed a sophia, using the writings and ideas of others. The contents of this sophia remain unclear. The witnesses accuse Pythagoras of foul trickery and plagiarism. Nevertheless, he must have produced some sort of systematic explanatory account of the world, its origin and its meaning. From the very beginning, both the "guru" and the "scholar" aspect are thus attested for Pythagoras. The content of the religious teachings is much more concrete than the content of Pythagoras's own philosophical and scientific doctrines. This trend continues as Riedweg examines later sources for the reconstruction of Pythagoras's ideas (chapter 2, section 3). As is already known, we get a relatively accurate picture of Pythagoras's position regarding rituals, lifestyle, and beliefs about the nature of the human soul (chapter 2, section 3, a-f), i.e., his ethical and religious [End Page 409] teachings. With regard to his contributions to science and philosophy, however, we are faced with the problem that we are no longer in the position to differentiate between early Pythagoreanism and Pythagoras himself—even if we leave the Platonic and the Platonist tradition out of the picture, and even where we can reconstruct details. Riedweg bases his outline predominantly on Aristotle's reports on pre-Platonic Pythagoreanism.Though Aristotle's evaluation rests mostly on Philolaus, the picture he develops for early Pythagoreanism throws some light also on Pythagoras himself. Riedweg thus uses Aristotle for an elucidation of a context for Pythagoras's contributions as a philosopher and scientist (chapter II, section 3, i). Another source of indirect information consists in comparisons with Orphic texts. Riedweg succeeds... (shrink)

Resumen: El corpus, siendo una herramienta eficaz, se está empleando en múltiples ámbitos, entre los que se encuentran los estudios de traducción. Sin embargo, dicho recurso no se utiliza con mucha frecuencia en las investigaciones traductológicas cuando una de las lenguas en cuestión es chino clásico (la lengua escrita empleada antiguamente en China), y autores que sí hacen estas investigaciones suelen no mencionar los pasos a seguir cuando se trata un corpus paralelo ad hoc. El objetivo del presente artículo es (...) presentar cómo se elabora un corpus paralelo chino clásico-español tomando como ejemplo la novela histórica Romance de los Tres Reinos y sus traducciones al español. Para ello, hemos descrito la problemática de creación y explotación de este tipo de corpus, siguiendo el orden de las fases del proceso. Resulta que algunas fases del proceso son universales, mientras que otras son propias de lenguas clásicas y de la combinación lingüística chino-otra lengua, en cuyo caso sí faltan aplicaciones eficaces. Con el trabajo, esperamos deparar información a los estudiosos que quieran realizar y profundizar las investigaciones basadas en corpus paralelo y en las obras clásicas de China. Abstract: The corpus, being an effective tool, is utilized in multiple fields. One of them is the Translation. However, this resource isn´t used frequently in translation studies when one of the languages in question is classical chinese (written language used anciently in China). And when it comes to an ad hoc parallel corpus, the steps of how to create it are usually omitted by researchers who make such investigations. The objective of this article is to present how to elaborate a classic Chinese-Spanish parallel corpus taking as example the historic novel Romance of the Three Kingdoms and its two translations into Spanish. To reach the objective, we have described the problem of creation and exploitation of this type of corpus, following the order of the phases of the process. We’ve found that some of the phases are universal while other phases are unique for old languages and for the linguistic combination Chinese-other language. And in this latter case, there’s a lack of effective applications. With the current work, we hope to offer useful information to those scholars who are willing to carry out their own investigations based on self-built parallel corpus and at the same time related to the classic Chinese works. (shrink)

The present study addresses language ostracism in intercultural communication, a phenomenon when someone speaks a language but some members of this language community don’t speak to him in this language. This phenomenon is illustrated by language behaviour towards visually distinct bilingual minorities in Taiwan. Visually distinct minorities in Taiwan reported that they had been spoken to in English by small children or people who did not believe and accept that they really understood Mandarin when they spoke it. They might be (...) spoken to in English despite actually speaking good Mandarin. Taiwanese people behave this way because of two conditions existing in Taiwan: an English-speaking foreigner stereotype where people assume that every foreign-looking person speaks English, and English privilege in Taiwanese society which leads to people being treated better if they can speak English. (shrink)

Thomas Polger and Lawrence Shapiro claim that unlike human-made artifacts cases of multiple realization in naturally occurring systems are uncommon. Drawing on cases from systems biology, I argue t...