In the recent past, several papers have pointed to the possibility that tumour removal generates a permissive environment in which tumour growth is potentiated. This phenomenon has been coined “perioperative tumour growth” and whilst it represents a departure in terms of our attitude to the surgical process, this concept was first hinted at by Paget1Sir James Paget (1814–1899) was a surgeon and physiologist who is widely held (along with Rudolph Virchow) to be the father of the science of pathology. Paget (...) described Paget's disease of the nipple as well as Paget's disease of bone. himself. Despite this, the time interval immediately before and after cancer surgery (i.e. the perioperative period) remains an underutilised interval during which chemotherapeutic regimens are rarely implemented. Herein, we present a summarised review of the literature that supports the concept that tumour removal may potentiate the growth of residual neoplastic disease. We also outline current knowledge regarding underlying mechanisms and in this manner highlight potential therapeutic entry points. Finally, we emphasise the urgent need for trials of agents that could protect patients against the harmful host–tumour interactions that may occur during the perioperative period. BioEssays 28: 433–437, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

This article examines one of the most crucial yet often-overlooked links in global film processes: piracy. It does so within the context of a changing digital media environment that calls for a reassessment of key dimensions: networks, globalization, technology, space and the state. More specifically, it focuses on the operation of film piracy networks in Greater China that includes the Mainland, Hong Kong and Taiwan. By zooming in on `Greater China', this article presents empirical accounts of specific links and connections (...) on and between the intersecting distribution and piracy networks. In sum, distribution and piracy in China highlight some of the most interesting and intricate insights into issues of power, control, technology, network, speed, global-regional-national dynamics, subjectivities and reflexivity. Given the complexity of the issues, this study argues for a spatial, network and process-oriented theoretical framework. (shrink)

The RecA family proteins mediate homologous recombination, a ubiquitous mechanism for repairing DNA double‐strand breaks (DSBs) and stalled replication forks. Members of this family include bacterial RecA, archaeal RadA and Rad51, and eukaryotic Rad51 and Dmc1. These proteins bind to single‐stranded DNA at a DSB site to form a presynaptic nucleoprotein filament, align this presynaptic filament with homologous sequences in another double‐stranded DNA segment, promote DNA strand exchange and then dissociate. It was generally accepted that RecA family proteins function throughout (...) their catalytic cycles as right‐handed helical filaments with six protomers per helical turn. However, we recently reported that archaeal RadA proteins can also form an extended right‐handed filament with three monomers per helical turn and a left‐handed protein filament with four monomers per helical turn. Subsequent structural and functional analyses suggest that RecA family protein filaments, similar to the F1‐ATPase rotary motor, perform ATP‐dependent clockwise axial rotation during their catalytic cycles. This new hypothesis has opened a new avenue for understanding the molecular mechanism of RecA family proteins in homologous recombination. BioEssays 30:48–56, 2008. © 2007 Wiley Periodicals, Inc. (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)

In recent years, the construct of character has received substantial attention among developmental scientists, but no consensus exists about the content and structure of character, especially among children and early adolescents. In a study of positive development among racially diverse Cub Scouts in the greater Philadelphia area, we assessed the construct and concurrent validity of a new measure of character, the Assessment of Character in Children and Early Adolescents, among 906 Scouts and 775 non-Scout boys and girls. We identified an (...) eight-correlated-factor model as providing the best fit with our data. We further established measurement invariance and explored latent mean differences for ACCEA scores across two Scout groups, non-Scout boys and non-Scout girls. Girls were generally superior than boys on all character attributes. We further examined concurrent validity of ACCEA by correlating the character attributes with youth sense of school competence, intentional self-regulation and parental perception of youth school performance. We discuss implications for future character research and point to the value of the ACCEA measure being used by practitioners in character development programs. (shrink)

The second messenger molecules cAMP and Ca2+ regulate a large number of eukaryotic cellular events. cAMP acts on protein kinases and Ca2+ works through a ubiquitous calcium‐binding protein, calmodulin. The two systems are not independent, however, but interact in several important fashions. These interactions, and, in particular, the modulation of the cAMP signal by two Ca2+/calmodulin‐regulated proteins, cyclic nucleotide phosphodiesterase and calcineurin, are described here.

Recent magnetic resonance imaging and pathological studies have indicated that axonal loss is a major contributor to disease progression in multiple sclerosis. 1 H magnetic resonance spectroscopy, through measurement of N -acetyl aspartate, a neuronal marker, provides a unique tool to investigate this. Patients with primary progressive multiple sclerosis have few lesions on conventional MRI, suggesting that changes in normal appearing white matter, such as axonal loss, may be particularly relevant to disease progression in this group. To test this hypothesis (...) NAWM was studied with MRS, measuring the concentration of N -acetyl derived groups. Single-voxel MRS using a water-suppressed PRESS sequence was carried out in 24 patients with primary progressive multiple sclerosis and in 16 age-matched controls. Ratios of metabolite to creatine concentration were calculated in all subjects, and absolute concentrations were measured in 18 patients and all controls. NA/Cr was significantly lower in NAWM in patients than in controls, as was the absolute concentration of NA. There was no significant difference in the absolute concentration of creatine between the groups. This study supports the hypothesis that axonal loss occurs in NAWM in primary progressive multiple sclerosis and may well be a mechanism for disease progression in this group. (shrink)

As understanding of the human microbiome improves, novel therapeutic targets to improve human health with microbial therapeutics will continue to expand. We outline key considerations of balancing risks and benefits, optimising access, returning key results to research participants, and potential conflicts of interest.

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

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 contributions to this special collection concern issues and problems discussed in or related to the work of Wesley C. Salmon. Salmon has long been noted for his important work in the philosophy of science, which has included research on the interpretation of probability, the nature of explanation, the character of reasoning, the justification of induction, the structure of space/time and the paradoxes of Zeno, to mention only some of the most prominent. During a time of increasing preoccupation with historical (...) and sociological approaches to under standing science (which characterize scientific developments as though they could be adequately analysed from the perspective of political movements, even mistaking the phenomena of conversion for the rational appraisal of scientific theories), Salmon has remained stead fastly devoted to isolating and justifying those normative standards distinguishing science from non-science - especially through the vindi cation of general principles of scientific procedure and the validation of specific examples of scientific theories - without which science itself cannot be (even remotely) adequately understood. In this respect, Salmon exemplifies and strengthens a splendid tradi tion whose most remarkable representatives include Hans Reichenbach, Rudolf Carnap and Carl G. Hempel, all of whom exerted a profound influence upon his own development. (shrink)

Truth and Meaning is a classic collection of original essays on fundamental questions in the philosophy of language. It was first published in 1976, and has remained essential reading in this area ever since. The contributors include leading figures in late twentieth-century philosophy, such as Donald Davidson, Saul Kripke, P. F. Strawson, and Michael Dummett.

My object in this paper is to suggest a few reflections on some themes in Bentham's work which others as well as (and even more than) I have noted, without perhaps developing them as fully as might with advantage be done. There will be nothing like full development in the limited compass of what is said here, but what is said may at least indicate possible directions for further exploration. The greater part of the paper will be concerned with the (...) notion of natural authority; but I want to begin by taking a broader, though no doubt rather superficial, view of the role in Bentham's thinking of the concepts of ‘nature’ and ‘the natural’. (shrink)

State of nature theories have a long history and play a lively role in contemporary work. Theories of this kind share certain nontrivial commitments. Among these are commitments to inclusion of a Lockean proviso among the principles of justice and to an assumption of invariance of political principles across changes of circumstances. In this article I want to look at those two commitments and bring to light what I believe are some important difficulties they engender. For nonpattern state of nature (...) theories, the justness of a society is marked by the conformance of the society to procedural principles. Distributions of resources and the like have no particular import for questions of justice. Whatever may later result, so long as it came about in accordance with the rules determined by the principles of justice, is itself just. The Lockean proviso is one of the principles of justice governing property and other rights of nonpattern theories of justice. The proviso hangs as a "shadow" over the results of the operation of the other (usual) principles of justice. It is intended to remedy a complaint which arises when the positions of those no longer at liberty to use some resource are worsened (1) by no longer being able to use freely what they previously were free to use and (2) in such a way that they fall below a "baseline." Following Locke, a traditional formulation of the proviso is to allow acquisition just so long as there is "enough and as good" left over for others. Section I concerns the relation of the Lockean proviso to pattern and nonpattern principles of justice, demonstrating that a Lockean proviso turns a nonpattern into a pattern theory of justice. Section II is about the relation of the Lockean proviso to the ideas revealed by an examination of a state of nature, suggesting reasons to reject ideal theories of justice. (shrink)

Philoxenus of Cythera's dithyramb, Cyclops or Galatea, was a poem famous in antiquity as the source for the story of Polyphemus' love for the sea-nymph Galatea. The exact date of composition is uncertain, but the poem must pre-date 388 B.C., when it was parodied by Aristophanes in the parodos of Plutus , and probably, as we shall see below, post-dates 406, the point at which Dionysius I became tyrant of Syracuse . The Aristophanic parody of the work may well point (...) to a recent performance in Athens, perhaps the first, and it is hard to identify any more significant reason for mentioning the poem. Previous accounts of the poem have concentrated on two main points, its supposed satirical purpose, and the possibly dramatic nature of its performance, but there has been no attempt to consider these two points in relation to each other, or to assess in detail the value of the source-material. I argue that although there is some evidence to support the satirical reading of the poem, the main value of this tradition is that it reveals Philoxenus' comic treatment of his subject, and that while the Galatea motif has previously been considered the essential element in this comic treatment, it was probably a small part of the plot, perhaps only briefly alluded to. Finally I provide reasons for doubting the prevalent view that the performance included dramatic elements. (shrink)

This essay considers the nature of duties incumbent on legislators in virtue of the office itself. I argue that there is no duty for a legislator to enact a criminal law based on morality; there is no duty to incorporate substantive moral conditions into the criminal law; and there is therefore no duty derivable from the nature of the legislative office itself to make conditions of culpability depend on those of moral responsibility. Finally, I argue that the relation between morality (...) and the criminal law is therefore much less direct than assumed in most theories of the criminal law. (shrink)

This lecture is divided, roughly, into three parts. First, there is a general and perhaps rather simple-minded discussion of what are the ‘facts’ that social anthropologists study; is there anything special about these ‘facts’ which makes them different from other kinds of facts? It will be useful to start with the common-sense distinction between two kinds or, better, aspects of social facts; first—though neither is analytically prior to the other—and putting it very crudely, ‘what people do’, the aspect of social (...) interaction, and second, ‘what—and how—people think’, the conceptual, classifying, cognitive component of human culture. Now in reality, of course (and perhaps not so ‘of course’; people do tend to think of them as separate ‘things’), these two aspects are inextricably intertwined. But it is essential to distinguish them analytically, because each aspect gives rise to quite different kinds of problems of understanding for the social anthropologist. We shall see that the problem of how to be ‘objective’, and so to avoid ethnographic error, arises in both contexts, but in rather different forms in each. (shrink)