Pathprinting: An integrative approach to understand the functional basis of disease

New strategies to combat complex human disease require systems approaches to biology that integrate experiments from cell lines, primary tissues and model organisms. We have developed Pathprint, a functional approach that compares gene expression profiles in a set of pathways, networks and transcriptionally regulated targets. It can be applied universally to gene expression profiles across species. Integration of large-scale profiling methods and curation of the public repository overcomes platform, species and batch effects to yield a standard measure of functional distance between experiments. We show that pathprints combine mouse and human blood developmental lineage, and can be used to identify new prognostic indicators in acute myeloid leukemia. The code and resources are available at http://​compbio.​sph.​harvard.​edu/​hidelab/​pathprin

Toroidal Magnetic Fields in Type II Superconducting Neutron Stars

We determine constraints on the form of axisymmetric toroidal magnetic fields dictated by hydrostatic balance in a type II superconducting neutron star with a barotropic equation of state. Using Lagrangian perturbation theory, we find the quadrupolar distortions due to such fields for various models of neutron stars with type II superconducting and normal regions. We find that the star becomes prolate and can be sufficiently distorted to display precession with a period of the order of years. We also study the stability of such fields using an energy principle, which allows us to extend the stability criteria established by R. J. Tayler for normal conductors to more general media with magnetic free energy that depends on density and magnetic induction, such as type II superconductors. We also derive the growth rate and instability conditions for a specific instability of type II superconductors, first discussed by P. Muzikar, C. J. Pethick and P. H. Roberts, using a local analysis based on perturbations around a uniform background.Comment: 32 pages, 6 figures; derivations shortened, comments and references added; accepted for publication in MNRA

Prediction of infrared light emission from pi-conjugated polymers: a diagrammatic exciton basis valence bond theory

There is currently a great need for solid state lasers that emit in the infrared, as this is the operating wavelength regime for applications in telecommunications. Existing $\pi$--conjugated polymers all emit in the visible or ultraviolet, and whether or not $\pi$--conjugated polymers that emit in the infrared can be designed is an interesting challenge. On the one hand, the excited state ordering in trans-polyacetylene, the $\pi$--conjugated polymer with relatively small optical gap, is not conducive to light emission because of electron-electron interaction effects. On the other hand, excited state ordering opposite to that in trans-polyacetylene is usually obtained by chemical modification that increases the effective bond-alternation, which in turn increases the optical gap. We develop a theory of electron correlation effects in a model $\pi$-conjugated polymer that is obtained by replacing the hydrogen atoms of trans-polyacetylene with transverse conjugated groups, and show that the effective on-site correlation in this system is smaller than the bare correlation in the unsubstituted system. An optical gap in the infrared as well as excited state ordering conducive to light emission is thereby predicted upon similar structural modifications.Comment: 15 pages, 15 figures, 1 tabl

An extended massless phase and the Haldane phase in a spin-1 isotropic antiferromagnetic chain

We study the phase transition of isotropic spin-1 models in the vicinity of the Uimin-Lai-Sutherland model by using the SU(3)_1 WZW model with certain marginal perturbations. The unstable RG trajectory by a marginally relevant perturbation generates a mass gap for the Haldane phase, and thus the universality class of the transition from the massless phase to the Haldane phase at ULS point becomes the BKT type. Our results support recent numerical studies by F\'ath and S\'olyom. In the massless phase, we calculate logarithmic finite-size corrections of the energy for the SU(\nu)-symmetric and asymmetric models.Comment: 19 pages, RevTe

Madang Province: Text summaries, maps, code lists and village identification

The major purpose of the Papua New Guinea Agricultural Systems Project is to produce information on small holder (subsistence) agriculture at provincial and national levels (Allen et al 1995). Information was collected by field observation, interviews with villagers and reference to published and unpublished documents. Methods are described by Bourke et al. (1993). This Working Paper contains a written summary of the information on the Agricultural Systems in this Province, maps of the location of agriculture systems, a complete listing of all information in the database in coded form, and lists of villages with National Population Census codes, indexed by agricultural systems. This information is available as a map-linked database (GIS) suitable for use on a personal computer in ESRI and MapInfo formats. An Agricultural System is identified when a set of similar agricultural crops and practices occur within a defined area. Six criteria are used to distinguish one system from another: 1. Fallow type (the vegetation which is cleared from a garden site before cultivation). 2. Fallow period (the length of time a garden site is left unused between cultivations). 3. Cultivation intensity (the number of consecutive crops planted before fallow). 4. The staple, or most important, crops. 5. Garden and crop segregation (the extent to which crops are planted in separate gardens; in separate areas within a garden; or are planted sequentially). 6. Soil fertility maintenance techniques (other than natural regrowth fallows). Where one or more of these factors differs significantly and the differences can be mapped, then a separate system is distinguished. Where variation occurs, but is not able to be mapped at 1:500 000 scale because the areas in which the variation occurs are too small or are widely dispersed within the larger system, a subsystem is identified. Subsystems within an Agricultural System are allocated a separate record in the database, identified by the Agricultural System number and a subsystem number. Sago is a widespread staple food in lowland Papua New Guinea. Sago is produced from palms which are not grown in gardens. Most of the criteria above cannot be applied. In this case, systems are differentiated on the basis of the staple crops only. The Papua New Guinea Resource Information System (PNGRIS) is a GIS which contains information on the natural resources of PNG (Bellamy 1986). PNGRIS contains no information on agricultural practices, other than an assessment of land use intensity based on air photograph interpretation by Saunders (1993. The Agricultural Systems Project is designed to provide detailed information on agricultural practices and cropping patterns as part of an upgraded PNGRIS geographical information system. For this reason the Agricultural Systems database contains almost no information on the environmental settings of the systems, except for altitude and slope. The layout of the text descriptions, the database code files and the village lists are similar to PNGRIS formats (Cuddy 1987). The mapping of Agricultural Systems has been carried out on the same map base and scale as PNGRIS (Tactical Pilotage Charts, 1:500 000). Agricultural Systems were mapped within the areas of agricultural land use established by Saunders (1993) from aerial photography. Except where specifically noted, Agricultural Systems boundaries have been mapped without reference to PNGRIS Resource Mapping Unit (RMU) boundaries. Agricultural Systems are defined at the level of the Province (following PNGRIS) but their wider distribution is recognised in the database by cross-referencing systems which cross provincial borders. A preliminary view of the relationships between PNGRIS RMUs and the Agricultural Systems in this Province can be obtained from the listing of villages by Agricultural System, where RMU numbers are appended. Allen, B. J., R. M. Bourke and R. L. Hide 1995. The sustainability of Papua New Guinea agricultural systems: the conceptual background. Global Environmental Change 5(4): 297-312. Bourke, R. M., R. L. Hide, B. J. Allen, R. Grau, G. S. Humphreys and H. C. Brookfield 1993. Mapping agricultural systems in Papua New Guinea. Population Family Health and Development. T. Taufa and C. Bass. University of Papua New Guinea Press, Port Moresby: 205-224. Bellamy, J. A. and J. R. McAlpine 1995. Papua New Guinea Inventory of Natural Resources, Population Distribution and Land Use Handbook. Commonwealth Scientific and Industrial Research Organisation for the Australian Agency for International Development. PNGRIS Publication No. 6, Canberra. Cuddy, S. M. 1987. Papua New Guinea Inventory of Natural Resources, Population Distribution and Land Use: Code Files Part 1 Natural Resources. Division of Water and Land Resources, Commonwealth Scientific and Industrial Research Organisation and Land Utilization Section, Department of Primary Industry, Papua New Guinea, Canberra

Relationship between photonic band structure and emission characteristics of a polymer distributed feedback laser

G. A. Turnbull, P. Andrew, M. J. Jory, William L. Barnes, and I. D. W. Samuel, Physical Review B, Vol. 64, article 125122 (2001). "Copyright © 2001 by the American Physical Society."We present an experimental study of the emission characteristics and photonic band structure of a distributed feedback polymer laser, based on the material poly[2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylene vinylene]. We use measurements of the photonic band dispersion to explain how the substrate microstructure modifies both spontaneous and stimulated emission. The lasing structure exhibits a one-dimensional photonic band gap around 610 nm, with lasing occurring at one of the two associated band edges. The band edge (frequency) selection mechanism is found to be a difference in the level of output coupling of the modes associated with the two band edges. This is a feature of the second-order distributed feedback mechanism we have employed and is clearly evident in the measured photonic band structur

Mesoscopic Cooperative Emission From a Disordered System

We study theoretically the cooperative light emission from a system of $N\gg 1$ classical oscillators confined within a volume with spatial scale, $L$, much smaller than the radiation wavelength, $\lambda_0=2\pi c/\omega_0$. We assume that the oscillators frequencies are randomly distributed around a central frequency, $\omega_0$, with some characteristic width, $\Omega\ll\omega_0$. In the absence of disorder, that is $\Omega=0$, the cooperative emission spectrum is composed of a narrow subradiant peak superimposed on a wide superradiant band. When $\Omega\neq 0$, we demonstrate that if $N$ is large enough, the subradiant peak is not simply broadened by the disorder but rather splits into a system of random narrow peaks. We estimate the spectral width of these peaks as a function of $N, L, \Omega$, and $\lambda_0$. We also estimate the amplitude of this mesoscopic structure in the emission spectrum.Comment: 25 pages including 6 figure

A Network of Epigenetic Regulators Guide Developmental Hematopoiesis In Vivo

The initiation of cellular programs is orchestrated by key transcription factors and chromatin regulators that activate or inhibit target gene expression. To generate a compendium of chromatin factors that establish the epigenetic code during developmental hematopoiesis, a large-scale reverse genetic screen was conducted targeting orthologs of 425 human chromatin factors in zebrafish. A set of chromatin regulators was identified that target different stages of primitive and definitive blood formation, including factors not previously implicated in hematopoiesis. We identified 15 factors that regulate development of primitive erythroid progenitors and 29 factors that regulate development of definitive stem and progenitor cells. These chromatin factors are associated with SWI/SNF and ISWI chromatin remodeling, SET1 methyltransferase, CBP/P300/HBO1/NuA4 acetyltransferase, HDAC/NuRD deacetylase, and Polycomb repressive complexes. Our work provides a comprehensive view of how specific chromatin factors and their associated complexes play a major role in the establishment of hematopoietic cells in vivo

Using molecular data for epidemiological inference: assessing the prevalence of Trypanosoma brucei rhodesiense in Tsetse in Serengeti, Tanzania

Background: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. Methodology/Principal Findings: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0–0.085) for G. swynnertoni and 0% (0–0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0–0.054) and 0.0089% (0–0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. Conclusions/Significance: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data

Photonic mode dispersion of a two-dimensional distributed feedback polymer laser

G. A. Turnbull, P. Andrew, William L. Barnes, and I. D. W. Samuel, Physical Review B, Vol. 67, article 165107 (2003). "Copyright © 2003 by the American Physical Society."We present an analysis of the photonic mode dispersion of a two-dimensional (2D) distributed feedback polymer laser based on the conjugated polymer poly[2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylene vinylene]. We use a combination of a simple model, together with experimental measurements of the photonic mode dispersion in transmission and emission, to explain the operating characteristics of the laser. The laser was found to oscillate at 636 nm on one edge of a photonic stop band in the photonic dispersion. A 2D coupling of modes traveling perpendicular to the orthogonal gratings was found to lead to a low divergence laser emission normal to the waveguide. At pump energies well above the oscillation threshold for this mode, a divergent, cross-shaped far-field emission was observed, resulting from a distributed feedback occurring over a wide range of wave vectors in one band of the photonic dispersion