Nested Hierarchical Dirichlet Processes

We develop a nested hierarchical Dirichlet process (nHDP) for hierarchical topic modeling. The nHDP is a generalization of the nested Chinese restaurant process (nCRP) that allows each word to follow its own path to a topic node according to a document-specific distribution on a shared tree. This alleviates the rigid, single-path formulation of the nCRP, allowing a document to more easily express thematic borrowings as a random effect. We derive a stochastic variational inference algorithm for the model, in addition to a greedy subtree selection method for each document, which allows for efficient inference using massive collections of text documents. We demonstrate our algorithm on 1.8 million documents from The New York Times and 3.3 million documents from Wikipedia.Comment: To appear in IEEE Transactions on Pattern Analysis and Machine Intelligence, Special Issue on Bayesian Nonparametric

The Emergence of Captive Finance Companies and Risk Segmentation of the Consumer Loan Market:Theory and Evidence

A parental seller with market power to some degree in its product market can earn rents. In this context, there is a gain to granting credit for the purchase of the product and thus the establishment of captive finance company for expanding the sales by offering loans to consumers who need financing for purchase of durable good. This paper examines the optimal behavior of such a durable good seller and its captive finance company when the consumer loan market is segmented into captive and independent lending institutions under symmetric and imperfect information on borrower’s creditworthiness. The model presents that one critical difference for captive finance company will be its credit standard. Specifically, the model indicates that captive finance company will follow a more lenient credit standard, leading to the prediction that the likelihood of repayment of a captive loan is lower than that of a bank loan, other things equal. This prediction is tested using unique data sets drawn from a major credit bureau in the U.S. The analysis of credit bureau data shows that a captive automobile loan is less likely to be repaid than a bank automobile loan, which supports the theoretical prediction.Monopolistic Competition, Consumer Loan Market, Captive Finance Company, Differential Loan Performances

Gain Modulation by Corticostriatal and Thalamostriatal Input Signals during Reward-Conditioned Behavior.

The cortex and thalamus send excitatory projections to the striatum, but little is known about how these inputs, either individually or collectively, regulate striatal dynamics during behavior. The lateral striatum receives overlapping input from the secondary motor cortex (M2), an area involved in licking, and the parafascicular thalamic nucleus (PF). Using neural recordings, together with optogenetic terminal inhibition, we examine the contribution of M2 and PF projections on medium spiny projection neuron (MSN) activity as mice performed an anticipatory licking task. Each input has a similar contribution to striatal activity. By comparing how suppressing single or multiple projections altered striatal activity, we find that cortical and thalamic input signals modulate MSN gain and that this effect is more pronounced in a temporally specific period of the task following the cue presentation. These results demonstrate that cortical and thalamic inputs synergistically regulate striatal output during reward-conditioned behavior

Quasi-simultaneous multiplane calcium imaging of neuronal circuits

Two-photon excitation fluorescence microscopy is widely used to study the activity of neuronal circuits. However, the fast imaging is typically constrained to a single lateral plane for a standard microscope design. Given that cortical neuronal networks in a mouse brain are complex three-dimensional structures organised in six histologically defined layers which extend over many hundreds of micrometres, there is a strong demand for microscope systems that can record neuronal signalling in volumes. Henceforth, we developed a quasi-simultaneous multiplane imaging technique combining acousto-optic deflector and static remote focusing to provide fast imaging of neurons from different axial positions inside the cortical layers without the need for the mechanical interference of either the objective lens or the specimen. The hardware and the software are easily adaptable to existing two-photon microscopes. Here, we demonstrated that our imaging method can record, at high speed and high image contrast, the calcium dynamics of neurons in two different imaging planes separated axially, with the in-focus and the refocused planes 120 μm and 250 μm below the brain surface respectively

Genetic polymorphisms in chronic hyperplastic sinusitis with nasal polyposis

Objectives/Hypothesis: Although many proinflammatory cytokines have been identified in nasal polyp tissue, the initial trigger that causes this inflammation characterized by edema, lymphocytosis, and eosinophilia, is still unknown. The purpose of the present study is to identify the presence of genetic polymorphisms in proinflammatory, anti-inflammatory, and chemokine genes that might contribute to genetic susceptibility to chronic hyperplastic sinusitis with nasal polyposis (CHSwNP). Study Design: Case control study. Methods: Buccal swabs were taken from the left and right oral mucosal surfaces from 179 patients with CHSwNP and 153 nonpolyposis controls with the Purgene DNA purification protocol (Gentra). Genotyping assays for cytokine gene loci were performed on 14 cytokine genes using the iPlex Gold and the Mass Array Compact system (Sequenom, San Diego, CA). Tests of Hardy-Weinberg equilibrium proportions were performed separately in the cases and controls. Tests for evidence of association between alleles at each single-nucleotide polymorphism (SNP) and case-control status were performed using unconditional logistic regression. Results: The frequency of the A allele in a SNP located in tumor necrosis factor (TNF)-Α (rs1800629) is significantly different in patients with nasal polyposis versus controls without nasal polyposis, 18.6% and 11.5%, respectively with an individuals' odds of susceptibility to nasal polyps increasing almost two-fold (odds ratio, 1.86; confidence interval, 1.4–3.09) given at least one copy of the A allele at this SNP. All other cytokine gene polymorphisms of both inflammatory, anti-inflammatory, and chemokine genes were not statistically different between the two groups. Conclusions: TNF-Α-308, a SNP in the promoter region of this cytokine gene is associated with increased odds of developing nasal polyposis. TNF-Α is a potent immuno-mediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of this gene on the short arm of chromosome 6, with the major histocompatibility complex genes and complement, has raised the probability that polymorphism within this locus may contribute to a genetic association of this region of the genome with a wide variety of infectious and autoimmune diseases. Laryngoscope, 2009Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63071/1/20239_ftp.pd

Microscopic theory of glassy dynamics and glass transition for molecular crystals

We derive a microscopic equation of motion for the dynamical orientational correlators of molecular crystals. Our approach is based upon mode coupling theory. Compared to liquids we find four main differences: (i) the memory kernel contains Umklapp processes, (ii) besides the static two-molecule orientational correlators one also needs the static one-molecule orientational density as an input, where the latter is nontrivial, (iii) the static orientational current density correlator does contribute an anisotropic, inertia-independent part to the memory kernel, (iv) if the molecules are assumed to be fixed on a rigid lattice, the tensorial orientational correlators and the memory kernel have vanishing l,l'=0 components. The resulting mode coupling equations are solved for hard ellipsoids of revolution on a rigid sc-lattice. Using the static orientational correlators from Percus-Yevick theory we find an ideal glass transition generated due to precursors of orientational order which depend on X and p, the aspect ratio and packing fraction of the ellipsoids. The glass formation of oblate ellipsoids is enhanced compared to that for prolate ones. For oblate ellipsoids with X <~ 0.7 and prolate ellipsoids with X >~ 4, the critical diagonal nonergodicity parameters in reciprocal space exhibit more or less sharp maxima at the zone center with very small values elsewhere, while for prolate ellipsoids with 2 <~ X <~ 2.5 we have maxima at the zone edge. The off-diagonal nonergodicity parameters are not restricted to positive values and show similar behavior. For 0.7 <~ X <~ 2, no glass transition is found. In the glass phase, the nonergodicity parameters show a pronounced q-dependence.Comment: 17 pages, 12 figures, accepted at Phys. Rev. E. v4 is almost identical to the final paper version. It includes, compared to former versions v2/v3, no new physical content, but only some corrected formulas in the appendices and corrected typos in text. In comparison to version v1, in v2-v4 some new results have been included and text has been change

Three-phase four-leg flying-capacitor multi-level inverter-based active power filter for unbalanced current operation.

This study describes a new application of flying capacitor multi-level inverters whereby a three-phase, four-leg three-level inverter is used for harmonic current cancellation and unbalanced current compensation in a four-wire system. A direct three-dimensional-pulse-width modulation (3D-PWM) scheme is developed to deal with the increased state redundancy in the four-leg flying capacitor multi-level inverter. Test results show much superior performance in the four-leg case, which may allow the use of smaller DC supply capacitors. A new modified dead-beat current control algorithm is proposed and combined successfully with the 3D-PWM modulation technique in a hardware demonstrator of a complete active filter

An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo

Prophylactic vaccines for SARS-CoV-2 have lowered the incidence of severe COVID-19, but emergence of viral variants that are antigenically distinct from the vaccine strains are of concern and additional, broadly acting preventive approaches are desirable. Here, we report on a glycolipid termed 7DW8-5 that exploits the host innate immune system to enable rapid control of viral infections in vivo. This glycolipid binds to CD1d on antigen-presenting cells and thereby stimulates NKT cells to release a cascade of cytokines and chemokines. The intranasal administration of 7DW8-5 prior to virus exposure significantly blocked infection by three different authentic variants of SARS-CoV-2, as well as by respiratory syncytial virus and influenza virus, in mice or hamsters. We also found that this protective antiviral effect is both host-directed and mechanism-specific, requiring both the CD1d molecule and interferon-[Formula: see text]. A chemical compound like 7DW8-5 that is easy to administer and cheap to manufacture may be useful not only in slowing the spread of COVID-19 but also in responding to future pandemics long before vaccines or drugs are developed

Simulations of the Alternating Access Mechanism of the Sodium Symporter Mhp1

AbstractSodium coupled cotransporters of the five-helix inverted repeat (5HIR) superfamily use an alternating access mechanism to transport a myriad of small molecules across the cell membrane. One of the primary steps in this mechanism is the conformational transition from a state poised to bind extracellular substrates to a state that is competent to deliver substrate to the cytoplasm. Here, we construct a coarse-grained model of the 5HIR benzylhydantoin transporter Mhp1 that incorporates experimental structures of the outward- and inward-open states to investigate the mechanism of this conformational change. Using the weighted ensemble path-sampling method, we rigorously sample the outward- to inward-facing transition path ensemble. The transition path ensemble reveals a heterogeneous set of pathways connecting the two states and identifies two modes of transport: one consistent with a strict alternating access mechanism and another where decoupling of the inner and outer gates causes the transient formation of a continuous permeation pathway through the transporter. We also show that the conformational switch between the outward- and inward-open states results from rigid body motions of the hash motif relative to the substrate bundle, supporting the rocking bundle hypothesis. Finally, our methodology provides the groundwork for more chemically detailed investigations of the alternating mechanism