Biological Roles of Neural J Proteins

J proteins are chief regulators of the Hsp70 family, a highly conserved family of ATPases that mediate conformational changes in a broad range of proteins. The J protein family has been the central focus of numerous prokaryote and eukaryote biologists. Common questions that arise include: How does the J protein/Hsp70 machinery support protein folding? What role do J proteins play in protein misfolding and neurodegenerative disorders? Can the J protein/ Hsp70 machinery be harnessed to provide a rational basis for recombinant protein production? The current progress that has resulted from the convergence of biochemistry with Escherichia coli and Saccharomyces cerevisiae genetics has accelerated the pace at which these questions are being elucidated. We are beginning to gain some insights into the neuronal network of J proteins. Here, we highlight recent advances in our understanding of how select J proteins harness Hsp70 s for fundamentally important conformational work in neurons.     

肝再生

肝脏在受到损害或切除之后,可以显示出强大的再生能力。肝再生这一现象早已被人们发现并研究。肝脏再生的启动因素有哪些,又是如何适时终止的?在肝再生过程中,哪些基因的表达发生了变化?哪些信号通路参与了肝再生过程?这些问题一直是研究者关注的焦点。本文将对肝再生研究的这些热点问题进行综述。     

Interweaving categories: Styles,paradigms, and models

Analytical categories of scientific cultures have typically been used both exclusively and universally. For instance, when styles of scientific research are employed in attempts to understand and narrate science, styles alone are usually employed. This article is a thought experiment in interweaving categories. What would happen if rather than employ a single category, we instead investigated several categories simultaneously? What would we learn about the practices and theories, the agents and materials, and the political-technological impact of science if we analyzed and applied styles (à la Hacking and Crombie), paradigms (à la Kuhn), and models (à la van Fraassen and Cartwright) simultaneously? I address these questions in general and for a specific case study: a brief history of systematics.     

Border cases between autonomy and relevance: Economic sciences in Berlin—A natural experiment

The faculty of economics at today's Humboldt University in Berlin, as no other institution of economics, has witnessed three radical ruptures in its history: in 1933, National Socialism replaced the pluralism prevailing in the Weimar Republic by imposing a “German economics”; after WWII, GDR authorities replaced this NS regime by imposing a Marxist imperative, which after the fall of the wall was replaced by the Western standards of neoclassical economics. In reconstructing these three reforms, institutional history can serve as a context in which questions about the political nature of economic knowledge can be answered that remain speculative in a conceptual context. I thus present a natural experiment in the political epistemology of economics: How do economists respond to, resist, and stabilize, changing political regimes? How do economists renegotiate the autonomy of economic knowledge given changing demands as of its social task? Among others, I show that contrary to Robert Merton's old, but still widely held thesis in political epistemology—that the values of science are compatible only with democratic regimes—the totalitarian and authoritarian regimes created better conditions for methodological pluralism in economics than democratic society.     

A role for spatiotemporal scales in modeling

Bogen and Woodward's distinction between data and phenomena raises the need to understand the structure of the data-to-phenomena and theory-to-phenomena inferences. I suggest that one way to study the structure of these inferences is to analyze the role of the assumptions involved in the inferences: What kind of assumptions are they? How do these assumptions contribute to the practice of identifying phenomena? In this paper, using examples from atmospheric dynamics, I develop an account of the practice of identifying the target in the data-to-phenomena and theory-to-phenomena inferences in which assumptions about spatiotemporal scales play a central role in the identification of parameters that describe the target system. I also argue that these assumptions are not only empirical but they are also idealizing and abstracting. I conclude the paper with a reflection on the role of idealizations in modeling.     

‘Language,Truth and Reason’ 30 years later

This paper traces the origins of the styles project, originally presented as ‘styles of scientific reasoning’. ‘Styles of scientific thinking & doing’ is a better label; the styles can also be called genres, or, ways of finding out. A. C. Crombie’s template of six fundamentally distinct ones was turned into a philosophical tool, but with a tinge of Paul Feyerabend’s anarchism. Ways of finding out are not defined by necessary and sufficient conditions, but can be recognized as distinct within a sweeping, anthropological, vision of the European sciences. The approach is unabashedly whiggish. The emergence of these styles is part of what Reviel Netz calls cognitive history, and is to be understood in an ecological way. How did a species like ours, on an Earth like this, develop a few quite general strategies for finding out about, and altering, its world? At a more analytical level, the project invokes Bernard Williams’ notion of truthfulness to explicate the idea that these styles are ‘self-authenticating’ and without foundations. The paper concludes with open questions. What role (for example) have these few fundamentally distinct genres of inquiry played in the formation of the anomalous Western idea of Nature apart from Man?     

Brains as analog-model computers

Computational neuroscientists not only employ computer models and simulations in studying brain functions. They also view the modeled nervous system itself as computing. What does it mean to say that the brain computes? And what is the utility of the ‘brain-as-computer’ assumption in studying brain functions? In previous work, I have argued that a structural conception of computation is not adequate to address these questions. Here I outline an alternative conception of computation, which I call the analog-model. The term ‘analog-model’ does not mean continuous, non-discrete or non-digital. It means that the functional performance of the system simulates mathematical relations in some other system, between what is being represented. The brain-as-computer view is invoked to demonstrate that the internal cellular activity is appropriate for the pertinent information-processing (often cognitive) task.     

Quantitative genetics of zooplankton life histories

Quantitative genetic techniques are powerful tools for use in understanding the microevolutionary process. Because of their size, lifespan, and ease of culture, many zooplankton species are ideal for quantitative genetic approaches. As model systems, studies of zooplankton life histories are becoming increasingly used for examination of the central paradigms of evolutionary theory. Two of the fundamental empirical questions that zooplankton quantitative genetics studies can answer are: 1) How much genetic variance exists in natural populations for life history traits? 2) What is the empirical evidence for trade-offs that permeate life history theory based on optimality approaches? A review of existing data onDaphnia indicates substantial genetic variance for body size, clutch size, and age at first reproduction. Average broad-sense heritabilities for these three characters across 19 populations of 6 species are 0.31, 0.31, and 0.34, respectively. Although there is some discrepancy between the two pertinent studies that were designed to decompose the total genetic variance into its additive and non-additive components, a crude average seems to suggest that approximately 60% of the total genetic variance has an additive basis. The existing data are somewhat inconsistent with respect to presence/absence of trade-offs (negative genetic correlations) among life history traits. A composite of the existing data seems to argue against the existence of strong trade-offs between offspring size and offspring number, between present and future reproduction, and between developmental rate and fecundity. However, there is some evidence for a shift toward more negative (less positive) covariances in more stressful environments (e.g., low food). Zooplankton will prove to be very useful in future study in several important areas of research, including the genetics and physiology of aging, the importance of genotype-environment interaction for life history traits, and the evolution of phenotypic plasticity.     

Exponential smoothing: The state of the art

This paper is a critical review of exponential smoothing since the original work by Brown and Holt in the 1950s. Exponential smoothing is based on a pragmatic approach to forecasting which is shared in this review. The aim is to develop state-of-the-art guidelines for application of the exponential smoothing methodology. The first part of the paper discusses the class of relatively simple models which rely on the Holt-Winters procedure for seasonal adjustment of the data. Next, we review general exponential smoothing (GES), which uses Fourier functions of time to model seasonality. The research is reviewed according to the following questions. What are the useful properties of these models? What parameters should be used? How should the models be initialized? After the review of model-building, we turn to problems in the maintenance of forecasting systems based on exponential smoothing. Topics in the maintenance area include the use of quality control models to detect bias in the forecast errors, adaptive parameters to improve the response to structural changes in the time series, and two-stage forecasting, whereby we use a model of the errors or some other model of the data to improve our initial forecasts. Some of the major conclusions: the parameter ranges and starting values typically used in practice are arbitrary and may detract from accuracy. The empirical evidence favours Holt's model for trends over that of Brown. A linear trend should be damped at long horizons. The empirical evidence favours the Holt-Winters approach to seasonal data over GES. It is difficult to justify GES in standard form–the equivalent ARIMA model is simpler and more efficient. The cumulative sum of the errors appears to be the most practical forecast monitoring device. There is no evidence that adaptive parameters improve forecast accuracy. In fact, the reverse may be true.     

Development of behavior and learning in Aplysia

A set of fundamental issues in neuroethology concerns the neural mechanisms underlying behavior and behavioral plasticity. We have recently analyzed these issues by combining a simple systems approach in the marine mollusc Aplysia with a developmental analysis aimed at examining the emergence and maturation of different forms of behavior and learning. We have focussed on two kinds of questions: 1) How are specific neural circuits developmentally assembled to mediate different types of behaviors? and 2) how is plasticity integrated with these circuits to give rise to different forms of learning? From our analysis of the development of learning and memory in Aplysia, several themes have emerged: 1) Different forms of learning emerge according to different developmental timetables. 2) Cellular analogs of learning have the same developmental timetables as their respective forms of behavioral learning. 3) An analysis of non-decremented responses prior to the emergence of sensitization reveals a novel inhibitory process on both behavioral and cellular levels. 4) Sensitization emerges simultaneously in diverse response systems, suggesting an underlying general process. 5) A widespread proliferation of central neurons occurs in the same developmental stage as the emergence of sensitization, raising the possibility that some aspect of the trigger for neuronal proliferation may also contribute to the expression of sensitization.     

Putting the Earth System in a numerical box? The evolution from climate modeling toward global change

Since the 1980s, climate modeling has undergone major transformations. The most prominent of these are the proliferation of coupled models and the integration within models of a growing number of environments and feedbacks. Climate modelers now increasingly define their object in terms of an “Earth System” instead of a “climate system”. In addition to this proliferation of coupled models, the carbon cycle and its feedback on various environments, from the atmosphere to the ocean and to vegetation cover, has become a prominent component of climate modeling. These transformations derive from the IPCC’s overall methodology, and are closely bound up with both a heightened awareness of the risks of climate change, as well as an issue of crucial political importance: the question of socio-economic/climate integration. In this article I follow, from a roughly chronological point of view, the major steps of this evolution and its links with the evolution of the political agenda. What can we say about this seemingly irreversible tendency to incorporate everything into models and to take account of everything that influences the Earth’s climate? Could we correlate it to the strong tendency toward globalization? How is the notion of climate itself affected? These are the main questions of the paper.     

Development of behavior and learning inAplysia

Summary A set of fundamental issues in neuroethology concerns the neural mechanisms underlying behavior and behavioral plasticity. We have recently analyzed these issues by combining a simple systems approach in the marine molluscAplysia with a developmental analysis aimed at examining the emergence and maturation of different forms of behavior and learning. We have focussed on two kinds of questions: 1) How are specific neural circuits developmentally assembled to mediate different types of behaviors? and 2) how is plasticity integrated with these circuits to give rise to different forms of learning? From our analysis of the development of learning and memory inAplysia, several themes have emerged: 1) Different forms of learning emerge according to different developmental timetables. 2) Cellular analogs of learning have the same developmental timetables as their respective forms of behavioral learing. 3) An analysis of non-decremented responses prior to the emergence of sensitization reveals a novel inhibitory process on both behavioral and cellular levels. 4) Sensitization emerges simultaneously in diverse response systems, suggesting an underlying general process. 5) A widespread proliferation of central neurons occurs in the same developmental stage as the emergence of sensitization, raising the possibility that some aspect of the trigger for neuronal proliferation may also contribute to the expression of sensitization.     

Cultures of simulations vs. cultures of calculations? The development of simulation practices in meteorology and astrophysics

While the distinction between theory and experiment is often used to discuss the place of simulation from a philosophical viewpoint, other distinctions are possible from a sociological perspective. Turkle (1995) distinguishes between cultures of calculation and cultures of simulation and relates these cultures to the distinction between modernity and postmodernity, respectively. What can we understand about contemporary simulation practices in science by looking at them from the point of view of these two computer cultures? What new questions does such an analysis raise for further studies? On the basis of two case studies, the present paper compares and discusses simulation activities in astrophysics and meteorology. It argues that simulation practices manifest aspects of both of these cultures simultaneously, but in different situations. By employing the dichotomies surface/depth, play/seriousness, and extreme/reasonable to characterize and operationalize cultures of calculation and cultures of simulation as sensitizing concepts, the analysis shows how simulation code work shifts from development to use, the importance of but also resistance towards too much visualizations, and how simulation modelers play with extreme values, yet also try to achieve reasonable results compared to observations.     

State of the field: Latin American decolonial philosophies of science

Today, new histories of science are producing skeptical questions about the supposedly international philosophies of science that prevail in the North. The conceptual resources of such philosophies seem inadequate to enable them to interact effectively with how sciences and their philosophies do, could, and should function in today's economic, political, social and cultural, local and global contexts. How international, or universal, are these philosophies of science in reality? Here the focus will be on just one strain of these challenges. This one has emerged from Latin Americans who are creating anti-colonial histories and philosophies of knowledge production. They have named it modernity/coloniality/decolonial theory (MCD). They intend to develop a philosophy of science adequate for its own, Latin American needs. In the process, they transform typical Northern assumptions about modernity, its origins and its effects on Northern philosophies of science, as these are understood in both Latin America and around the globe.Five aspects of the MCD accounts will be discussed here. The first is historical differences between the worlds of the Spanish and Portuguese colonization of the Americas in the sixteenth century and of the worlds of the mostly British colonization of India and Africa in the ‘long nineteenth century’. Second is feminist and anti-racist issues in these Latin American histories. Third is the neglect of these histories in the North. Fourth is the continuing effects of the rise and fall of a positivist philosophy of science in Latin America. The fifth is two progressive post-positivist tensions for Northern philosophy of science produced in this work.     

Essentially narrative explanations

This essay argues that narrative explanations prove uniquely suited to answering certain explanatory questions, and offers reasons why recognizing a type of statement that requires narrative explanations crucially informs on their assessment. My explication of narrative explanation begins by identifying two interrelated sources of philosophical unhappiness with them. The first I term the problem of logical formlessness and the second the problem of evaluative intractability. With regard to the first, narratives simply do not appear to instantiate any logical form recognized as inference licensing. But absent a means of identifying inferential links, what justifies connecting explanans and explanandum? Evaluative intractability, the second problem, thus seems a direct consequence. This essay shows exactly why these complaints prove unfounded by explicating narrative explanations in the process of answering three interrelated questions. First, what determines that an explanation has in some critical or essential respect a narrative form? Second, how does a narrative in such cases come to constitute a plausible explanation? Third, how do the first two considerations yield a basis for evaluating an explanation offered as a narrative? Answers to each of these questions include illustrations of actual narrative explanations and also function to underline attendant dimensions of evaluation.     

Is there a cost to being socially responsible in investing?

In this study we address three questions concerning socially responsible investing. First, is the average return of a socially screened equity universe statistically different from the average return of an unscreened universe for the 1987–94 period? Second, do analysts' earnings per share forecasts aid a manager in selecting stocks in socially screened and unscreened universes? Third, can one use an expected return model incorporating both value and growth components to select stocks and create portfolios in the socially screened and unscreened equity universes such that one can outperform both universe benchmarks? We find no statistically significant differences in the mean returns of unscreened and screened equity universes for the 1987–94 period. Earnings forecasts and the knowledge of those forecasts add value in the creation of portfolios. We find few statistically significant differences in the predictive power of the composite model to select stocks in both unscreened and screened equity universes. The estimated composite model offers the potential for substantial outperformance of socially screened and unscreened equity universes. © 1997 John Wiley & Sons, Ltd.     

From centripetal forces to conic orbits: a path through the early sections of Newton’s Principia

In this study, we test the security of a crucial plank in the Principia’s mathematical foundation, namely Newton’s path leading to his solution of the famous Inverse Kepler Problem: a body attracted toward an immovable center by a centripetal force inversely proportional to the square of the distance from the center must move on a conic having a focus in that center. This path begins with his definitions of centripetal and motive force, moves through the second law of motion, then traverses Propositions I, II, and VI, before coming to an end with Propositions XI, XII, XIII and this trio’s first corollary. To test the security of this path, we answer the following questions. How far is Newton’s path from being truly rigorous? What would it take to clarify his ambiguous definitions and laws, supply missing details, and close logical gaps? In short, what would it take to make Newton’s route to the Inverse Kepler Problem completely convincing? The answer is very surprising: it takes far less than one might have expected, given that Newton carved this path in 1687.     

State of the field: Paper tools

Paper occupies a special place in histories of knowledge. It is the substrate of communication, the stuff of archives, the bearer of marks that make worlds. For the early-modern period in particular we now have a wealth of studies of ‘paper tools’, of the ways in which archives were assembled and put to use, of the making of lists and transcribing of observations, and so on. In other fields, too, attention has turned to the materiality of information. How far is it possible to draw a stable methodology out of the insights of literary and book historians, bibliographers, anthropologists, and those working in media studies? Do these diverse fields in fact refer to the same thing when they talk of paper, its qualities, affordances and limitations? In attempting to answer these questions, the present essay begins in the rich territory of early-modern natural philosophy – but from there opens out to take in recent works in a range of disciplines. Attending to the specific qualities of paper is only possible, I argue, if it is understood that paper can be both transparent and opaque depending on the social world it inhabits and helps to constitute. Paper flickers into and out of view, and it is precisely this quality that constitutes its sociomateriality.