Dissecting interferon-induced transcriptional programs in human peripheral blood cells

Interferons are key modulators of the immune system, and are central to the control of many diseases. The response of immune cells to stimuli in complex populations is the product of direct and indirect effects, and of homotypic and heterotypic cell interactions. Dissecting the global transcriptional profiles of immune cell populations may provide insights into this regulatory interplay. The host transcriptional response may also be useful in discriminating between disease states, and in understanding pathophysiology. The transcriptional programs of cell populations in health therefore provide a paradigm for deconvoluting disease-associated gene expression profiles.We used human cDNA microarrays to (1) compare the gene expression programs in human peripheral blood mononuclear cells (PBMCs) elicited by 6 major mediators of the immune response: interferons alpha, beta, omega and gamma, IL12 and TNFalpha; and (2) characterize the transcriptional responses of purified immune cell populations (CD4+ and CD8+ T cells, B cells, NK cells and monocytes) to IFNgamma stimulation. We defined a highly stereotyped response to type I interferons, while responses to IFNgamma and IL12 were largely restricted to a subset of type I interferon-inducible genes. TNFalpha stimulation resulted in a distinct pattern of gene expression. Cell type-specific transcriptional programs were identified, highlighting the pronounced response of monocytes to IFNgamma, and emergent properties associated with IFN-mediated activation of mixed cell populations. This information provides a detailed view of cellular activation by immune mediators, and contributes an interpretive framework for the definition of host immune responses in a variety of disease settings

The density matrix in the de Broglie-Bohm approach

If the density matrix is treated as an objective description of individual systems, it may become possible to attribute the same objective significance to statistical mechanical properties, such as entropy or temperature, as to properties such as mass or energy. It is shown that the de Broglie-Bohm interpretation of quantum theory can be consistently applied to density matrices as a description of individual systems. The resultant trajectories are examined for the case of the delayed choice interferometer, for which Bell appears to suggest that such an interpretation is not possible. Bell's argument is shown to be based upon a different understanding of the density matrix to that proposed here.Comment: 15 pages, 4 figure

The Science of Phylogenetic Systematics: Explanation, Prediction, and Test

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73926/1/j.1096-0031.1999.tb00279.x.pd

Entanglement and State Preparation

When a subset of particles in an entangled state is measured, the state of the subset of unmeasured particles is determined by the outcome of the measurement. This first measurement may be thought of as a state preparation for the remaining particles. In this paper, we examine how the duration of the first measurement effects the state of the unmeasured subsystem. The state of the unmeasured subsytem will be a pure or mixed state depending on the nature of the measurement. In the case of quantum teleportation we show that there is an eigenvalue equation which must be satisfied for accurate teleportation. This equation provides a limitation to the states that can be accurately teleported.Comment: 24 pages, 3 figures, submitted to Phys. Rev.

Encouraging versatile thinking in algebra using the computer

In this article we formulate and analyse some of the obstacles to understanding the notion of a variable, and the use and meaning of algebraic notation, and report empirical evidence to support the hypothesis that an approach using the computer will be more successful in overcoming these obstacles. The computer approach is formulated within a wider framework ofversatile thinking in which global, holistic processing complements local, sequential processing. This is done through a combination of programming in BASIC, physical activities which simulate computer storage and manipulation of variables, and specific software which evaluates expressions in standard mathematical notation. The software is designed to enable the user to explore examples and non-examples of a concept, in this case equivalent and non-equivalent expressions. We call such a piece of software ageneric organizer because if offers examples and non-examples which may be seen not just in specific terms, but as typical, or generic, examples of the algebraic processes, assisting the pupil in the difficult task of abstracting the more general concept which they represent. Empirical evidence from several related studies shows that such an approach significantly improves the understanding of higher order concepts in algebra, and that any initial loss in manipulative facility through lack of practice is more than made up at a later stage

Close Binary System GO Cyg

In this study, we present long term photometric variations of the close binary system \astrobj{GO Cyg}. Modelling of the system shows that the primary is filling Roche lobe and the secondary of the system is almost filling its Roche lobe. The physical parameters of the system are $M_1 = 3.0\pm0.2 M_{\odot}$, $M_2 = 1.3 \pm 0.1 M_{\odot}$, $R_1 = 2.50\pm 0.12 R_{\odot}$, $R_2 = 1.75 \pm 0.09 R_{\odot}$, $L_1 = 64\pm 9 L_{\odot}$, $L_2 = 4.9 \pm 0.7 L_{\odot}$, and $a = 5.5 \pm 0.3 R_{\odot}$. Our results show that \astrobj{GO Cyg} is the most massive system near contact binary (NCB). Analysis of times of the minima shows a sinusoidal variation with a period of $92.3\pm0.5$ years due to a third body whose mass is less than 2.3$M_{\odot}$. Finally a period variation rate of $-1.4\times10^{-9}$ d/yr has been determined using all available light curves.Comment: Accepted for publication in New Astronomy, 18 pages, 4 figures, 7 table

Gene-expression patterns reveal underlying biological processes in Kawasaki disease

Background: Kawasaki disease (KD) is an acute self-limited vasculitis and the leading cause of acquired heart disease in children in developed countries. No etiologic agent(s) has been identified, and the processes that mediate formation of coronary artery aneurysms and abatement of fever following treatment with intravenous immunoglobulin (IVIG) remain poorly understood. Results: In an initial survey, we used DNA microarrays to examine patterns of gene expression in peripheral whole blood from 20 children with KD; each was sampled during the acute, subacute, and convalescent phases of the illness. Acute KD was characterized by increased relative abundance of gene transcripts associated with innate immune and proinflammatory responses and decreased abundance of transcripts associated with natural killer cells and CD8+ lymphocytes. There was significant temporal variation in transcript levels during the acute disease phase and stabilization thereafter. We confirmed these temporal patterns in a second cohort of 64 patients, and identified additional inter-individual differences in transcript abundance. Notably, higher levels of transcripts of the gene for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) were associated with an increased percentage of unsegmented neutrophils, fewer days of illness, higher levels of C-reactive protein, and subsequent non-response to IVIG; this last association was confirmed by quantitative reverse transcription PCR in a third cohort of 33 patients, and was independent of day of illness. Conclusion: Acute KD is characterized by dynamic and variable gene-expression programs that highlight the importance of neutrophil activation state and apoptosis in KD pathogenesis. Our findings also support the feasibility of extracting biomarkers associated with clinical prognosis from gene-expression profiles of individuals with systemic inflammatory illnesses

Contracting for the unknown and the logic of innovation

This paper discusses the components of contracts adequatefor governing innovation, and their microfoundations in the logic of innovative decision processes. Drawing on models of discovery and design processes, distinctive logical features of innovative decision making are specified and connected to features of contracts that can sustain innovation processes and do not fail under radical uncertainty. It is argued that if new knowledge is to be generated under uncertainty and risk, 'relational contracts', as usually intended, are not enough and a more robust type of contracting is needed and it is actually often used: formal constitutional contracts that associate resources, leave their uses rationally unspecified, but exhaustively specify the assignment of residual decision rights and other property rights, and the decision rules to be followed in governance. The argument is supported by an analysis of a large international database on the governance of multi-party projects in discovery-intensive and design-intensive industries

An argument for the use of Aristotelian method in bioethics

The main claim of this paper is that the method outlined and used in Aristotle's Ethics is an appropriate and credible one to use in bioethics. Here “appropriate” means that the method is capable of establishing claims and developing concepts in bioethics and “credible” that the method has some plausibility, it is not open to obvious and immediate objection. It begins by suggesting why this claim matters and then gives a brief outline of Aristotle's method. The main argument is made in three stages. First, it is argued that Aristotelian method is credible because it compares favourably with alternatives. In this section it is shown that Aristotelian method is not vulnerable to criticisms that are made both of methods that give a primary place to moral theory (such as utilitarianism) and those that eschew moral theory (such as casuistry and social science approaches). As such, it compares favourably with these other approaches that are vulnerable to at least some of these criticisms. Second, the appropriateness of Aristotelian method is indicated through outlining how it would deal with a particular case. Finally, it is argued that the success of Aristotle's philosophy is suggestive of both the credibility and appropriateness of his method.</p

The u'g'r'i'z' Standard Star Network

We present the 158 standard stars that define the u'g'r'i'z' photometric system. These stars form the basis for the photometric calibration of the Sloan Digital Sky Survey (SDSS). The defining instrument system and filters, the observing process, the reduction techniques, and the software used to create the stellar network are all described. We briefly discuss the history of the star selection process, the derivation of a set of transformation equations for the UBVRcIc system, and plans for future work.Comment: References to URLs in paper have been updated to reflect moved website. Accepted by AJ. 50 pages, including 20 pages of text, 9 tables, and 15 figures. Plain ASCII text versions of Tables 8 and 9 can be found at http://home.fnal.gov/~dtucker/ugriz/index.html (new URL