Moving Ahead Amid Fiscal Challenges: A Look at Medicaid Spending, Coverage and Policy Trends

Examines fiscal year 2011 trends in state efforts to control Medicaid spending, reform payment and delivery systems, and prepare for healthcare reform implementation, as well as projections in spending and enrollment growth for fiscal year 2012

Modular combinatorial binding among human trans-acting factors reveals direct and indirect factor binding

Background The combinatorial binding of trans-acting factors (TFs) to the DNA is critical to the spatial and temporal specificity of gene regulation. For certain regulatory regions, more than one regulatory module (set of TFs that bind together) are combined to achieve context-specific gene regulation. However, previous approaches are limited to either pairwise TF co-association analysis or assuming that only one module is used in each regulatory region. Results We present a new computational approach that models the modular organization of TF combinatorial binding. Our method learns compact and coherent regulatory modules from in vivo binding data using a topic model. We found that the binding of 115 TFs in K562 cells can be organized into 49 interpretable modules. Furthermore, we found that tens of thousands of regulatory regions use multiple modules, a structure that cannot be observed with previous hard clustering based methods. The modules discovered recapitulate many published protein-protein physical interactions, have consistent functional annotations of chromatin states, and uncover context specific co-binding such as gene proximal binding of NFY + FOS + SP and distal binding of NFY + FOS + USF. For certain TFs, the co-binding partners of direct binding (motif present) differs from those of indirect binding (motif absent); the distinct set of co-binding partners can predict whether the TF binds directly or indirectly with up to 95% accuracy. Joint analysis across two cell types reveals both cell-type-specific and shared regulatory modules. Conclusions Our results provide comprehensive cell-type-specific combinatorial binding maps and suggest a modular organization of combinatorial binding. Keywords Computational genomics Transcription factor Combinatorial binding Direct and indirect binding Topic modelNational Institutes of Health (U.S.) (grant 1U01HG007037-01

The Crunch Continues: Medicaid Spending, Coverage and Policy in the Midst of a Recession

Presents results from a state-by-state Medicaid budget survey for fiscal years 2009 and 2010. Examines the effects of the recession on spending, how states used Medicaid fiscal relief funds from the federal stimulus package, and the outlook for 2011

Training Data Attribution for Diffusion Models

Diffusion models have become increasingly popular for synthesizing high-quality samples based on training datasets. However, given the oftentimes enormous sizes of the training datasets, it is difficult to assess how training data impact the samples produced by a trained diffusion model. The difficulty of relating diffusion model inputs and outputs poses significant challenges to model explainability and training data attribution. Here we propose a novel solution that reveals how training data influence the output of diffusion models through the use of ensembles. In our approach individual models in an encoded ensemble are trained on carefully engineered splits of the overall training data to permit the identification of influential training examples. The resulting model ensembles enable efficient ablation of training data influence, allowing us to assess the impact of training data on model outputs. We demonstrate the viability of these ensembles as generative models and the validity of our approach to assessing influence.Comment: 14 pages, 6 figure

Low Medicaid Spending Growth Amid Rebounding State Revenues: Results From a 50-State Medicaid Budget Survey State Fiscal Years 2006 and 2007

Examines the implementation of the new Medicare prescription drug benefit and the rate of Medicaid spending growth and enrollment in 2006. Identifies possible state level changes in eligibility requirements, program expansion, and enrollment processes

Vortex lattice stability and phase coherence in three-dimensional rapidly rotating Bose condensates

We establish the general equations of motion for the modes of a vortex lattice in a rapidly rotating Bose-Einstein condensate in three dimensions, taking into account the elastic energy of the lattice and the vortex line bending energy. As in two dimensions, the vortex lattice supports Tkachenko and gapped sound modes. In contrast, in three dimensions the Tkachenko mode frequency at long wavelengths becomes linear in the wavevector for any propagation direction out of the transverse plane. We compute the correlation functions of the vortex displacements and the superfluid order parameter for a homogeneous Bose gas of bounded extent in the axial direction. At zero temperature the vortex displacement correlations are convergent at large separation, but at finite temperatures, they grow with separation. The growth of the vortex displacements should lead to observable melting of vortex lattices at higher temperatures and somewhat lower particle number and faster rotation than in current experiments. At zero temperature a system of large extent in the axial direction maintains long range order-parameter correlations for large separation, but at finite temperatures the correlations decay with separation.Comment: 10 pages, 2 figures, Changes include the addition of the particle density - vortex density coupling and the correct value of the shear modulu

Hierarchical Dirichlet Process-Based Models For Discovery of Cross-species Mammalian Gene Expression

An important research problem in computational biology is theidentification of expression programs, sets of co-activatedgenes orchestrating physiological processes, and thecharacterization of the functional breadth of these programs. Theuse of mammalian expression data compendia for discovery of suchprograms presents several challenges, including: 1) cellularinhomogeneity within samples, 2) genetic and environmental variationacross samples, and 3) uncertainty in the numbers of programs andsample populations. We developed GeneProgram, a new unsupervisedcomputational framework that uses expression data to simultaneouslyorganize genes into overlapping programs and tissues into groups toproduce maps of inter-species expression programs, which are sortedby generality scores that exploit the automatically learnedgroupings. Our method addresses each of the above challenges byusing a probabilistic model that: 1) allocates mRNA to differentexpression programs that may be shared across tissues, 2) ishierarchical, treating each tissue as a sample from a population ofrelated tissues, and 3) uses Dirichlet Processes, a non-parametricBayesian method that provides prior distributions over numbers ofsets while penalizing model complexity. Using real gene expressiondata, we show that GeneProgram outperforms several popularexpression analysis methods in recovering biologically interpretablegene sets. From a large compendium of mouse and human expressiondata, GeneProgram discovers 19 tissue groups and 100 expressionprograms active in mammalian tissues. Our method automaticallyconstructs a comprehensive, body-wide map of expression programs andcharacterizes their functional generality. This map can be used forguiding future biological experiments, such as discovery of genesfor new drug targets that exhibit minimal "cross-talk" withunintended organs, or genes that maintain general physiologicalresponses that go awry in disease states. Further, our method isgeneral, and can be applied readily to novel compendia of biologicaldata

Dislocation-Mediated Melting in Superfluid Vortex Lattices

We describe thermal melting of the two-dimensional vortex lattice in a rotating superfluid by generalizing the Halperin and Nelson theory of dislocation-mediated melting. and derive a melting temperature proportional to the renormalized shear modulus of the vortex lattice. The rigid-body rotation of the superfluid attenuates the effects of lattice compression on the energy of dislocations and hence the melting temperature, while not affecting the shearing. Finally, we discuss dislocations and thermal melting in inhomogeneous rapidly rotating Bose-Einstein condensates; we delineate a phase diagram in the temperature -- rotation rate plane, and infer that the thermal melting temperature should lie below the Bose-Einstein transition temperature.Comment: 9 pages, 2 figure