Majorities of Californians Support the Nation's New Health Care Law, but Think More Health Care System Changes Are Needed

Analyzes Californians' views on the 2010 healthcare reform law, including the need for further reform, concerns about the state's healthcare system, and preferred source of coverage by political affiliation, insurance status, education, and demographics

Ancient eukaryotic origin and evolutionary plasticity of nuclear lamina

The emergence of the nucleus was a major event of eukaryogenesis. How the nuclear envelope (NE) arose and acquired functions governing chromatin organization and epigenetic control has direct bearing on origins of developmental/stage-specific expression programs. The configuration of the NE and the associated lamina in the last eukaryotic common ancestor (LECA) is of major significance and can provide insight into activities within the LECA nucleus. Subsequent lamina evolution, alterations and adaptations inform on the variation and selection of distinct mechanisms that subtend gene expression in distinct taxa. Understanding lamina evolution has been difficult due to the diversity and limited taxonomic distributions of the three currently known highly distinct nuclear lamina. We rigorously searched available sequence data for an expanded view of the distribution of known lamina and lamina-associated proteins. Whilst the lamina proteins of plants and trypanosomes are indeed taxonomically restricted, homologs of metazoan lamins and key lamin-binding proteins have significantly broader distributions, and a lamin gene tree supports vertical evolution from the LECA. Two protist lamins from highly divergent taxa target the nucleus in mammalian cells and polymerise into filamentous structures, suggesting functional conservation of distant lamin homologs. Significantly, a high level of divergence of lamin homologs within certain eukaryotic groups and the apparent absence of lamins and/or the presence of seemingly different lamina proteins in many eukaryotes suggests great evolutionary plasticity in structures at the NE, and hence mechanisms of chromatin tethering and epigenetic gene control

An automated graphics tool for comparative genomics: the Coulson plot generator.

BACKGROUND: Comparative analysis is an essential component to biology. When applied to genomics for example, analysis may require comparisons between the predicted presence and absence of genes in a group of genomes under consideration. Frequently, genes can be grouped into small categories based on functional criteria, for example membership of a multimeric complex, participation in a metabolic or signaling pathway or shared sequence features and/or paralogy. These patterns of retention and loss are highly informative for the prediction of function, and hence possible biological context, and can provide great insights into the evolutionary history of cellular functions. However, representation of such information in a standard spreadsheet is a poor visual means from which to extract patterns within a dataset. RESULTS: We devised the Coulson Plot, a new graphical representation that exploits a matrix of pie charts to display comparative genomics data. Each pie is used to describe a complex or process from a separate taxon, and is divided into sectors corresponding to the number of proteins (subunits) in a complex/process. The predicted presence or absence of proteins in each complex are delineated by occupancy of a given sector; this format is visually highly accessible and makes pattern recognition rapid and reliable. A key to the identity of each subunit, plus hierarchical naming of taxa and coloring are included. A java-based application, the Coulson plot generator (CPG) automates graphic production, with a tab or comma-delineated text file as input and generating an editable portable document format or svg file. CONCLUSIONS: CPG software may be used to rapidly convert spreadsheet data to a graphical matrix pie chart format. The representation essentially retains all of the information from the spreadsheet but presents a graphically rich format making comparisons and identification of patterns significantly clearer. While the Coulson plot format is highly useful in comparative genomics, its original purpose, the software can be used to visualize any dataset where entity occupancy is compared between different classes. AVAILABILITY: CPG software is available at sourceforge http://sourceforge.net/projects/coulson and http://dl.dropbox.com/u/6701906/Web/Sites/Labsite/CPG.html.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Activation of endocytosis as an adaptation to the mammalian host by trypanosomes

Immune evasion in African trypanosomes is principally mediated by antigenic variation, but rapid internalization of surface-bound immune factors may contribute to survival. Endocytosis is upregulated approximately 10-fold in bloodstream compared to procyclic forms, and surface coat remodeling accompanies transition between these life stages. Here we examined expression of endocytosis markers in tsetse fly stages in vivo and monitored modulation during transition from bloodstream to procyclic forms in vitro. Among bloodstream stages nonproliferative stumpy forms have endocytic activity similar to that seen with rapidly dividing slender forms, while differentiation of stumpy forms to procyclic forms is accompanied by rapid down-regulation of Rab11 and clathrin, suggesting that modulation of endocytic and recycling systems accompanies this differentiation event. Significantly, rapid down-regulation of endocytic markers occurs upon entering the insect midgut and expression of Rab11 and clathrin remains low throughout subsequent development, which suggests that high endocytic activity is not required for remodeling the parasite surface or for survival within the fly. However, salivary gland metacyclic forms dramatically increase expression of clathrin and Rab11, indicating that emergence of mammalian infective forms is coupled to reacquisition of a high-activity endocytic-recycling system. These data suggest that high-level endocytosis in Trypanosoma brucei is an adaptation required for viability in the mammalian host

Extracting information from the signature of a financial data stream

Market events such as order placement and order cancellation are examples of the complex and substantial flow of data that surrounds a modern financial engineer. New mathematical techniques, developed to describe the interactions of complex oscillatory systems (known as the theory of rough paths) provides new tools for analysing and describing these data streams and extracting the vital information. In this paper we illustrate how a very small number of coefficients obtained from the signature of financial data can be sufficient to classify this data for subtle underlying features and make useful predictions. This paper presents financial examples in which we learn from data and then proceed to classify fresh streams. The classification is based on features of streams that are specified through the coordinates of the signature of the path. At a mathematical level the signature is a faithful transform of a multidimensional time series. (Ben Hambly and Terry Lyons \cite{uniqueSig}), Hao Ni and Terry Lyons \cite{NiLyons} introduced the possibility of its use to understand financial data and pointed to the potential this approach has for machine learning and prediction. We evaluate and refine these theoretical suggestions against practical examples of interest and present a few motivating experiments which demonstrate information the signature can easily capture in a non-parametric way avoiding traditional statistical modelling of the data. In the first experiment we identify atypical market behaviour across standard 30-minute time buckets sampled from the WTI crude oil future market (NYMEX). The second and third experiments aim to characterise the market "impact" of and distinguish between parent orders generated by two different trade execution algorithms on the FTSE 100 Index futures market listed on NYSE Liffe

Phosphoinositides, kinases and adaptors coordinating endocytosis in Trypanosoma brucei

In the kinetoplastid parasite Trypanosoma brucei clathrin-mediated endocytosis is essential for survival and aids immune evasion in the mammalian host. The formation of endocytic clathrin coated vesicles in T. brucei is via a unique mechanism owing to an evolutionarily recent loss of the adaptor protein (AP)2 complex, a central hub in endocytic vesicle assembly. Despite this loss, recent studies examining endocytic clathrin coat assembly have highlighted a high degree of conservation between trypanosomes and their mammalian hosts. In particular phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) and its putative effectors, TbCALM and TbEpsinR, are central to clathrin-mediated endocytosis in the trypanosome, just as they are in animal cells. In addition to providing insights into the cell biology of T. brucei, these studies also suggest an ancient, possibly pan-eukaryotic connection between PtdIns(4,5)P(2) and endocytosis

Rab23 is a flagellar protein in Trypanosoma brucei.

BACKGROUND: Rab small GTPases are important mediators of membrane transport, and orthologues frequently retain similar locations and functions, even between highly divergent taxa. In metazoan organisms Rab23 is an important negative regulator of Sonic hedgehog signaling and is crucial for correct development and differentiation of cellular lineages by virtue of an involvement in ciliary recycling. Previously, we reported that Trypanosoma brucei Rab23 localized to the nuclear envelope 1, which is clearly inconsistent with the mammalian location and function. As T. brucei is unicellular the potential that Rab23 has no role in cell signaling was possible. Here we sought to further investigate the role(s) of Rab23 in T. brucei to determine if Rab23 was an example of a Rab protein with divergent function in distinct taxa. METHODS/MAJOR FINDINGS: The taxonomic distribution of Rab23 was examined and compared with the presence of flagella/cilia in representative taxa. Despite evidence for considerable secondary loss, we found a clear correlation between a conventional flagellar structure and the presence of a Rab23 orthologue in the genome. By epitope-tagging, Rab23 was localized and found to be present at the flagellum throughout the cell cycle. However, RNAi knockdown did not result in a flagellar defect, suggesting that Rab23 is not required for construction or maintenance of the flagellum. CONCLUSIONS: The location of Rab23 at the flagellum is conserved between mammals and trypanosomes and the Rab23 gene is restricted to flagellated organisms. These data may suggest the presence of a Rab23-mediated signaling mechanism in trypanosomes.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A Surrogate Model of Gravitational Waveforms from Numerical Relativity Simulations of Precessing Binary Black Hole Mergers

We present the first surrogate model for gravitational waveforms from the coalescence of precessing binary black holes. We call this surrogate model NRSur4d2s. Our methodology significantly extends recently introduced reduced-order and surrogate modeling techniques, and is capable of directly modeling numerical relativity waveforms without introducing phenomenological assumptions or approximations to general relativity. Motivated by GW150914, LIGO's first detection of gravitational waves from merging black holes, the model is built from a set of $276$ numerical relativity (NR) simulations with mass ratios $q \leq 2$, dimensionless spin magnitudes up to $0.8$, and the restriction that the initial spin of the smaller black hole lies along the axis of orbital angular momentum. It produces waveforms which begin $\sim 30$ gravitational wave cycles before merger and continue through ringdown, and which contain the effects of precession as well as all $\ell \in \{2, 3\}$ spin-weighted spherical-harmonic modes. We perform cross-validation studies to compare the model to NR waveforms \emph{not} used to build the model, and find a better agreement within the parameter range of the model than other, state-of-the-art precessing waveform models, with typical mismatches of $10^{-3}$. We also construct a frequency domain surrogate model (called NRSur4d2s_FDROM) which can be evaluated in $50\, \mathrm{ms}$ and is suitable for performing parameter estimation studies on gravitational wave detections similar to GW150914.Comment: 34 pages, 26 figure