M-CSF instructs myeloid lineage fate in single haematopoietic stem cells

Under stress conditions such as infection or inflammation the body rapidly needs to generate new blood cells that are adapted to the challenge. Haematopoietic cytokines are known to increase output of specific mature cells by affecting survival, expansion and differentiation of lineage-committed progenitors, but it has been debated whether long-term haematopoietic stem cells (HSCs) are susceptible to direct lineage-specifying effects of cytokines. Although genetic changes in transcription factor balance can sensitize HSCs to cytokine instruction, the initiation of HSC commitment is generally thought to be triggered by stochastic fluctuation in cell-intrinsic regulators such as lineage-specific transcription factors, leaving cytokines to ensure survival and proliferation of the progeny cells. Here we show that macrophage colony-stimulating factor (M-CSF, also called CSF1), a myeloid cytokine released during infection and inflammation, can directly induce the myeloid master regulator PU.1 and instruct myeloid cell-fate change in mouse HSCs, independently of selective survival or proliferation. Video imaging and single-cell gene expression analysis revealed that stimulation of highly purified HSCs with M-CSF in culture resulted in activation of the PU.1 promoter and an increased number of PU.1(+) cells with myeloid gene signature and differentiation potential. In vivo, high systemic levels of M-CSF directly stimulated M-CSF-receptor-dependent activation of endogenous PU.1 protein in single HSCs and induced a PU.1-dependent myeloid differentiation preference. Our data demonstrate that lineage-specific cytokines can act directly on HSCs in vitro and in vivo to instruct a change of cell identity. This fundamentally changes the current view of how HSCs respond to environmental challenge and implicates stress-induced cytokines as direct instructors of HSC fate

A Soluble Phase Field Model

The kinetics of an initially undercooled solid-liquid melt is studied by means of a generalized Phase Field model, which describes the dynamics of an ordering non-conserved field phi (e.g. solid-liquid order parameter) coupled to a conserved field (e.g. thermal field). After obtaining the rules governing the evolution process, by means of analytical arguments, we present a discussion of the asymptotic time-dependent solutions. The full solutions of the exact self-consistent equations for the model are also obtained and compared with computer simulation results. In addition, in order to check the validity of the present model we confronted its predictions against those of the standard Phase field model and found reasonable agreement. Interestingly, we find that the system relaxes towards a mixed phase, depending on the average value of the conserved field, i.e. on the initial condition. Such a phase is characterized by large fluctuations of the phi field.Comment: 13 pages, 8 figures, RevTeX 3.1, submitted to Physical Review

Uniform random generation of large acyclic digraphs

Directed acyclic graphs are the basic representation of the structure underlying Bayesian networks, which represent multivariate probability distributions. In many practical applications, such as the reverse engineering of gene regulatory networks, not only the estimation of model parameters but the reconstruction of the structure itself is of great interest. As well as for the assessment of different structure learning algorithms in simulation studies, a uniform sample from the space of directed acyclic graphs is required to evaluate the prevalence of certain structural features. Here we analyse how to sample acyclic digraphs uniformly at random through recursive enumeration, an approach previously thought too computationally involved. Based on complexity considerations, we discuss in particular how the enumeration directly provides an exact method, which avoids the convergence issues of the alternative Markov chain methods and is actually computationally much faster. The limiting behaviour of the distribution of acyclic digraphs then allows us to sample arbitrarily large graphs. Building on the ideas of recursive enumeration based sampling we also introduce a novel hybrid Markov chain with much faster convergence than current alternatives while still being easy to adapt to various restrictions. Finally we discuss how to include such restrictions in the combinatorial enumeration and the new hybrid Markov chain method for efficient uniform sampling of the corresponding graphs.Comment: 15 pages, 2 figures. To appear in Statistics and Computin

Quantum critical point and scaling in a layered array of ultrasmall Josephson junctions

We have studied a quantum Hamiltonian that models an array of ultrasmall Josephson junctions with short range Josephson couplings, $E_J$, and charging energies, $E_C$, due to the small capacitance of the junctions. We derive a new effective quantum spherical model for the array Hamiltonian. As an application we start by approximating the capacitance matrix by its self-capacitive limit and in the presence of an external uniform background of charges, $q_x$. In this limit we obtain the zero-temperature superconductor-insulator phase diagram, $E_J^{\rm crit}(E_C,q_x)$, that improves upon previous theoretical results that used a mean field theory approximation. Next we obtain a closed-form expression for the conductivity of a square array, and derive a universal scaling relation valid about the zero--temperature quantum critical point. In the latter regime the energy scale is determined by temperature and we establish universal scaling forms for the frequency dependence of the conductivity.Comment: 18 pages, four Postscript figures, REVTEX style, Physical Review B 1999. We have added one important reference to this version of the pape

Universal relations in the finite-size correction terms of two-dimensional Ising models

Quite recently, Izmailian and Hu [Phys. Rev. Lett. 86, 5160 (2001)] studied the finite-size correction terms for the free energy per spin and the inverse correlation length of the critical two-dimensional Ising model. They obtained the universal amplitude ratio for the coefficients of two series. In this study we give a simple derivation of this universal relation; we do not use an explicit form of series expansion. Moreover, we show that the Izmailian and Hu's relation is reduced to a simple and exact relation between the free energy and the correlation length. This equation holds at any temperature and has the same form as the finite-size scaling.Comment: 4 pages, RevTeX, to appear in Phys. Rev. E, Rapid Communication

Assessing Preliminary Impact of the North Carolina Community Transformation Grant Project Farmers' Market Initiatives Among Rural Residents

Objective: Using the Social Determinants of Health as the study's theoretical underpinning, the authors examined the impact of the North Carolina Community Transformation Grant Project farmers' market initiatives on changes in awareness and use of farmers' markets, and fruit and vegetable consumption. Methods: During the farmers' market season, the researchers conducted a random digit-dial telephone survey among residents in 3 rural North Carolina counties to examine changes in farmers' market awareness, shopping, and fruit and vegetable consumption. They examined change over 1 year using t tests, chi-square tests, and propensity score matching. Results: In 1 county there were increases in farmers' market shopping and fruit and vegetable consumption, and in 1 county there were decreases in farmers' market shopping and fruit and vegetable consumption. Conclusions and Implications: The impact of farmers' market initiatives may be affected by county-specific socioeconomic contexts

Relativistic Calculation of the Meson Spectrum: a Fully Covariant Treatment Versus Standard Treatments

A large number of treatments of the meson spectrum have been tried that consider mesons as quark - anti quark bound states. Recently, we used relativistic quantum "constraint" mechanics to introduce a fully covariant treatment defined by two coupled Dirac equations. For field-theoretic interactions, this procedure functions as a "quantum mechanical transform of Bethe-Salpeter equation". Here, we test its spectral fits against those provided by an assortment of models: Wisconsin model, Iowa State model, Brayshaw model, and the popular semi-relativistic treatment of Godfrey and Isgur. We find that the fit provided by the two-body Dirac model for the entire meson spectrum competes with the best fits to partial spectra provided by the others and does so with the smallest number of interaction functions without additional cutoff parameters necessary to make other approaches numerically tractable. We discuss the distinguishing features of our model that may account for the relative overall success of its fits. Note especially that in our approach for QCD, the resulting pion mass and associated Goldstone behavior depend sensitively on the preservation of relativistic couplings that are crucial for its success when solved nonperturbatively for the analogous two-body bound-states of QED.Comment: 75 pages, 6 figures, revised content

Availability of Farmers’ Markets and Supplemental Nutrition Assistance Program/Electronic Benefit Transfer Systems and Associations With Rurality, Poverty, Race/Ethnicity, and Obesity Among North Carolina Counties

Increasing the number of farmers’ markets and implementing Electronic Benefit Transfer (EBT) systems for the Supplemental Nutrition Assistance Program (SNAP) at more farmers’ markets have been suggested as strategies to overcome food access issues, but little is known about their availability in the rural South. This study examines differences in availability of farmers’ markets and SNAP/EBT at markets by county-level rural/urban classification, percentage poverty, percentage racial/ethnic minority, and percentage obese residents in North Carolina counties. Data were collected using a cross-sectional survey. Though results related to rurality and economic status are mixed, regression analyses indicate that the percentage of African American residents is inversely associated with the number of markets and number of markets that accept EBT. Results suggest that access to farmers’ markets varies in North Carolina, and additional research is needed to determine whether this impacts obesity

First record of Rhabdoceras suessi (Ammonoidea, Late Triassic) from the Transylvanian Triassic Series of the Eastern Carpathians (Romania) and a review of its biochronology, paleobiogeography and paleoecology

Abstract The occurrence of the heteromorphic ammonoid Rhabdoceras suessi Hauer, 1860, is recorded for the first time in the Upper Triassic limestone of the Timon-Ciungi olistolith in the Rarău Syncline, Eastern Carpathians. A single specimen of Rhabdoceras suessi co-occurs with Monotis (Monotis) salinaria that constrains its occurrence here to the Upper Norian (Sevatian 1). It is the only known heteromorphic ammonoid in the Upper Triassic of the Romanian Carpathians. Rhabdoceras suessi is a cosmopolitan species widely recorded in low and mid-paleolatitude faunas. It ranges from the Late Norian to the Rhaetian and is suitable for high-resolution worldwide correlations only when it co-occurs with shorter-ranging choristoceratids, monotid bivalves, or the hydrozoan Heterastridium. Formerly considered as the index fossil for the Upper Norian (Sevatian) Suessi Zone, by the latest 1970s this species lost its key biochronologic status among Late Triassic ammonoids, and it generated a controversy in the 1980s concerning the status of the Rhaetian stage. New stratigraphic data from North America and Europe in the subsequent decades resulted in a revised ammonoid biostratigraphy for the uppermost Triassic, the Rhaetian being reinstalled as the topmost stage in the current standard timescale of the Triassic. The geographic distribution of Rhabdoceras is compiled from published worldwide records, and its paleobiogeography and paleoecology are discussed