Variations in levels of apolipoprotein E have been tied to the risk and progression of Alzheimer's disease . Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter's role in the human disease. We examine here three specific single-nucleotide polymorphisms within the human APOE promoter region, specifically at -491 , -427 , and at -219 upstream from the (...) +1 transcription start site. The -219 and -491 polymorphic variations have significant association with instance of AD, and -491AA has significant risk even when stratified for the APOEepsilon4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The -491 and -219 polymorphisms may have an interactive effect in addition to any independent activity. DNA-protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the -491 and -219 polymorphic sites. This work's significance lies in drawing connection among APOE promoter polymorphisms' associations with AD to functional promoter activity differences and specific changes in DNA-protein interactions in cell culture-based assays. Taken together, these results suggest that APOE expression levels are a risk factor for AD irrespective of APOEepsilon4 allele status. (shrink)

Understanding terrestrial carbon metabolism is critical because terrestrial ecosystems play a major role in the global carbon cycle. Furthermore, humans have severely disrupted the carbon cycle in ways that will alter the climate system and directly affect terrestrial metabolism. Changes in terrestrial metabolism may well be as important an indicator of global change as the changing temperature signal. Improving our understanding of the carbon cycle at various spatial and temporal scales will require the integration of multiple, complementary and independent methods (...) that are used by different research communities. Tools such as air sampling networks, inverse numerical methods, and satellite data allow us to study the strength and location of the global- and continental-scale carbon sources and sinks. Bottom-up studies provide estimates of carbon fluxes at finer spatial scales and examine the mechanisms that control fluxes at the ecosystem, landscape, and regional scales. Bottom-up approaches include comparative and process studies that provide the necessary mechanistic information to develop and validate terrestrial biospheric models. An iteration and reiteration of top-down and bottom-up approaches will be necessary to help constrain measurements at various scales. We propose a major international effort to coordinate and lead research programs of global scope of the carbon cycle. (shrink)

We report specific heat and μSR measurements on Th and/or B substituted UBe13. The specific heat data show that either Th or B substitution reduces the Kondo temperature TK and increases the entropy at the superconducting transition by almost 20%, indicating an enhanced density of states. However, whereas μSR shows clear evidence for magnetic correlations for Th substitutions, no magnetism is observed for B substitutions. The enhanced specific heat jump in the B-substituted material is associated with a change in the (...) superconducting properties as TK is reduced. (shrink)

The X-ray and bulk densities of PdIn alloys have been determined at ambient temperature on samples annealed at 1273 and 1373 K and quenched in water-ice mixtures. From these measurements the vacancy concentrations in this intermetallic phase have been obtained as a function of In concentration at these two temperatures. In addition, a generalized thermodynamic model is presented which considers the existence of antisite and vacancy defects on both sublattices without any dilute solution approximations. This model uses three energy parameters, (...) whose values have been obtained for PdIn using the measured vacancy concentrations and the chemical potentials of In. This model is able to describe all the available vacancy data and is suitable for calculating these values at compositions and temperatures when such data are not available. In addition, the model permits the calculation of the concentrations of the minority point defects. It is shown that dilute-solution approximations, which have invariably been used in this kind of modelling, are unsatisfactory. The present results and their analysis confirm that PdIn is a near-triple-defect type of intermetallic and not a near-Schottky type, as has been claimed recently. (shrink)

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)

This article ana l yses the birth of some n e w female identities in Latin America, mar k e d b y strong cultural inn o v ation. The process of change has been w on b y political st r uggles that h a v e pe r mitted Latin American w omen to g ain some essential rights. More o v er the t e x t describes the compl e xity of syncretising all Lati n America, (...) but the common elements are more important than the di f ferences. H o w e v e r , accepting this d i v ersit y , the great inequality of basic essentials in the relationships be t w een w omen, is producing one v oice, one discourse and one common demand. F inal l y , it sh o ws the political contradictions in w hich contempora ry Latin America w omen l i v e, summoned to pa r ticipate, as mode r n w omen, in the institutions w hen these same institutions put them in positions of social, political and economic subordination. Despite these di f f iculties, it emphasises the political e xperiments that w omen are ca r r ying out to f ind a syncretism without eliminating cultural d i versit y. (shrink)

Education is so strongly emphasized in the Chinese culture that academic success is widely regarded as the only indicator of success, while too much physical activity is often discouraged because it drains energy and affects academic concentration. This study investigated the relations among academic achievement, self?esteem, school conduct and physical activity level. The participants were 333 Chinese pre?adolescents (aged 8?12) in Hong Kong. Examination results and conduct grades were obtained from the school records. Global self?esteem was measured with the Physical (...) self?description questionnaire (PSDQ), while physical activity patterns of the children were assessed with the Physical activity questionnaire for children (PAQ?C). Results showed that high academic achievers consistently attained better school conduct marks. However, physical activity level was quite an independent entity that was related neither to academic achievement nor school conduct. Furthermore, regression analyses showed that only academically high?achieving boys and physically active boys had higher self?esteem. (shrink)

A change in sense of self is an outcome commonly associated with Buddhist meditation. However, the sense of self is construed in multiple ways, and which changes in self-related processing are expected, intended, or possible through meditation is not well understood. In a qualitative study of meditation-related challenges, six discrete changes in sense of self were reported by Buddhist meditators: change in narrative self, loss of sense of ownership, loss of sense of agency, change in sense of embodiment, change in (...) self-other or self-world boundaries, and loss of sense of basic self. Changes in sense of self could be transient or enduring, positive or distressing, enhancing or impairing. These changes were also given varied appraisals, ranging from insights associated with Buddhist doctrines to psychopathologies such as depersonalization. In this study of practitioners reporting meditation-related challenges, more global changes in sense of self were associated with higher levels of impairment. These results have implications for both Buddhist meditation as well as mindfulness-based interventions. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:J. H. Hexter 1910–1996Donald R. KelleyJ. H. Hexter, one of the leading intellectual historians of this century and a close associate of this Journal, died on 8 December 1996. Jack Hexter was a great scholar, talented writer and polemicist, devoted baseball fan, and authentic American humorist, who made wit and facetiousness part of his historiographical tool-kit. He was also an American character, as he made insistently clear in his (...) writings, especially his autobiographical account, “By Any Other Name,” which explained (among other things) why he came to be called “Jack,” why he resisted advice to change it, and other onomastic adventures.Jack taught at Queens College (N.Y., not, he pointed out, the one in South Carolina), 1939–57; Washington University (St. Louis, not Seattle or George Washington U.), 1957–64 and again 1978–86; and Yale University (one did not have to add, “New Haven”) 1965–85, where he was Director of the Center for Parliamentary History. At Washington University he was founding Director of the Center for the History of Freedom, which was devoted to a collaborative, multi-volume study of the history of liberty in the West that would realize the dream that Lord Acton called his “madonna of the future”—the difference being that Jack’s vision is already on the way to fulfillment, with the publication of the volume edited by him on Parliament and Liberty from the Reign of Elizabeth to the English Civil War (1992), followed by seven more volumes up to 1996, with more to come.Hexter published books and articles in a variety of fields, finding notoriety especially in his essay of 1958, “Storm over the Gentry,” and later in public jousts with Christopher Hill and others and more retrospective censures of (among others) A. W. Pollard and R. H. Tawney; and he was a master of the Macaulayan art of the review-essay (collected in On Historians, 1979). His article on “Braudel and le monde braudelien” was a mischievous masterpiece of satire which, according to a private communication to Jack, Braudel himself enjoyed in his Olympian way, including the good-natured charge of excessive appetite for facts—“Je vais me dire: ne joue pas trop au Rabelais, sois sage, ne mange pas tout, n’aie les yeux plus gros que le ventre!” (personal letter, 8 February 1973). Several generations of graduate students learned what was involved in doing history from his “The Historian and his Day” (1954), which (like “Storm”), he enjoyed recalling, was rejected by the AHR. He was amused, too, at learning that his article on “The Rhetoric of History” (written for the International Encyclopedia of the Social Sciences) was a harbinger of the rhetorical turn taken a few years later signalled by the historiographical work of Hayden White and others. He was a pioneer, too, in the intensive study of political languages (Visions of Politics on the Eve of the Reformation, 1973), though he lamented the fact that his work on Machiavelli’s and Seyssel’s political vocabulary had to be carried out before the age of computer technology.My first contact with Jack came through my mentor Garrett Mattingly, who was the contemporary historian Jack “most admired” (as he made plain in his contribution to Mattingly’s festschrift). In 1962 Mattingly told me that the plan to publish Hexter’s translation of Seyssel’s Monarchy of France for the Columbia Records Series had to be abandoned because of the first (I think) of Jack’s several heart attacks. I was able to use the mimeographed version for some years before Jack asked me to take over this project, originally visited on him by C. H. McIlwain. It was his suggestion that [End Page 349] we dedicate the collaborative volume, with nice ambiguity, to both McIlwain and Mattingly (who had also been a student of McIlwain) from “two of their deeply devoted students.”In this brief and perhaps overpersonal note (though nothing could be “too personal” for Jack) I will not add further to the store of Hexterian anecdotes, which I began collecting at Queens College, where Jack had already left the makings of a legend in the 1950s. I would just add... (shrink)

Originally published 1972.This book concerns the progressive movement, its prominent thinkers and its achievements, at a period of vital change in English primary education. The role of progressive educationists, such as Lane, Neill and Montessori is considered. The author asserts that these pioneers gradually made themselves the intellectual orthodoxy in the years between the wars.

This book examines how enlightened Scottish social theorists c.1740 to c.1800 understood the origin and development of religion. Challenging scholarly disregard for the topic, it shows how most prominent thinkers of the Scottish Enlightenment thought deeply about the relationship between religion, human nature and historical change. The Scots viewed this relationship as an important strand within the study of the 'science of human nature' and the 'history of man.' The fruits of this investigation were a sophisticated and innovative account of (...) religious change that is characterized by a striking modernity and naturalism, even by the more devout theorists. The views of the literati surveyed here need to be incorporated into our larger histories of the 'science of religion' as much as they do into our understanding of the social theory of the Scottish Enlightenment. (shrink)

In response to the increasingly popular manipulation argument against compatibilism, some have argued that libertarian accounts of free will are vulnerable to parallel manipulation arguments, and thus manipulation is not uniquely problematic for compatibilists. The main aim of this article is to give this point a more detailed development than it has previously received. Prior attempts to make this point have targeted particular libertarian accounts but cannot be generalized. By contrast, I provide an appropriately modified manipulation that targets all libertarian (...) accounts of freedom and responsibility—an especially tricky task given that libertarian accounts are a motley set. I conclude that if manipulation arguments reveal any theoretical cost then it is one borne by all accounts according to which we are free and responsible, not by compatibilism in particular. (shrink)

Objectives The objectives of the study are to understand the current practice of informed consent in medical research in public hospitals in Shanghai, and to share our views with other countries, especially developing countries. Methods In the study, 145 consent forms (CFs) of the selected research projects in eight public hospitals with ethics committees in Shanghai were audited, and the principle investigators (PIs) of these research projects and 40 student subjects who had participated in clinical drug tests were surveyed by (...) questionnaires. Results The CFs of medical researches in public hospitals with ethics committees in Shanghai were generally acceptable. However, there were some defects in the CFs. Although most of the surveyed PIs had correct recognition of informed consent, some processes of informed consent were not in accordance with generally accepted requirements. A large number of the PIs considered the greatest difficulty with informal consent was lack of correct recognition of subjects or legally authorised representatives on medical research. Discussion Informed consent in medical research should consider the research ethics, the background of potential subjects, the local resources and culture of medical research. In addition, special protection is needed for student subjects in informed consent as well as efforts for building and restoring the public's trust in biomedical research. Conclusion The informed consent in Shanghai's public hospitals with ethics committees was generally acceptable and the achievement of adequate informed consent is influenced by many factors. (shrink)

Background This paper describes the design, implementation, and process outcomes from three public deliberations held in three tribal communities. Although increasingly used around the globe to address collective challenges, our study is among the first to adapt public deliberation for use with exclusively Indigenous populations. In question was how to design deliberations for tribal communities and whether this adapted model would achieve key deliberative goals and be well received.Methods We adapted democratic deliberation, an approach to stakeholder engagement, for use with (...) three tribal communities to respect tribal values and customs. Public deliberation convenes people from diverse backgrounds in reasoned reflection and dialogue in search of collective solutions. The deliberation planning process and design were informed by frameworks of enclave deliberation and community-based participatory research, which share key egalitarian values. The deliberations were collaboratively designed with tribal leadership and extensive partner input and involvement in the deliberations. Each deliberation posed different, locally relevant questions about genomic research, but used the same deliberation structure and measures to gauge the quality and experience of deliberation.Results A total of 52 individuals participated in the deliberations across all three sites. Deliberants were balanced in gender, spanned decades in age, and were diverse in educational attainment and exposure to health research. Overall, the deliberations were positively evaluated. Participant perceptions and external observer datasets depict three deliberations that offered intensive conversation experiences in which participants learned from one another, reported feeling respected and connected to one another, and endorsed this intensive form of engagement.Conclusion The adapted deliberations achieved key deliberative goals and were generally well received. Limitations of the study are described. (shrink)

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5-6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor (...) evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation. (shrink)