The totally nonnegative Grassmannian is a ball

We prove that three spaces of importance in topological combinatorics are homeomorphic to closed balls: the totally nonnegative Grassmannian, the compactification of the space of electrical networks, and the cyclically symmetric amplituhedron.Comment: 19 pages. v2: Exposition improved in many place

Regularity theorem for totally nonnegative flag varieties

We show that the totally nonnegative part of a partial flag variety $G/P$ (in the sense of Lusztig) is a regular CW complex, confirming a conjecture of Williams. In particular, the closure of each positroid cell inside the totally nonnegative Grassmannian is homeomorphic to a ball, confirming a conjecture of Postnikov.Comment: 63 pages, 2 figures; v2: Minor changes; v3: Final version to appear in J. Amer. Math. So

Thoracic and lumbar vertebral bone mineral density changes in a natural occuring dog model of diffuse idiopathic skeletal hyperostosis

Ankylosing spinal disorders can be associated with alterations in vertebral bone mineral density (BMD). There is however controversy about vertebral BMD in patients wuse idiopathic skeletal hyperostosis (DISH). DISH in Boxer dogs has been considered a natural occurring disease model for DISH in people. The purpose of this study was to compare vertebral BMD between Boxers with and without DISH. Fifty-nine Boxers with (n=30) or without (n=29) DISH that underwent computed tomography were included. Vertebral BMD was calculated for each thoracic and lumbar vertebra by using an earlier reported and validated protocol. For each vertebral body, a region of interest was drawn on the axial computed tomographic images at three separate locations: immediately inferior to the superior end plate, in the middle of the vertebral body, and superior to the inferior end plate. Values from the three axial slices were averaged to give a mean Hounsfield Unit value for each vertebral body. Univariate statistical analysis was performed to identify factors to be included in a multivariate model. The multivariate model including all dogs demonstrated that vertebral DISH status (Coefficient 24.63; 95% CI 16.07 to 33.19; p < 0.001), lumbar vertebrae (Coefficient -17.25; 95% CI -23.42 to -11.09; p < 0.01), and to a lesser extent higher age (Coefficient -0.56; 95% CI -1.07 to -0.05; p = 0.03) were significant predictors for vertebral BMD. When the multivariate model was repeated using only dogs with DISH, vertebral DISH status (Coefficient 20.67; 95% CI, 10.98 to 30.37; p < 0.001) and lumbar anatomical region (Coefficient -38.24; 95% CI, -47.75 to -28.73; p < 0.001) were again predictors for vertebral BMD but age was not. The results of this study indicate that DISH can be associated with decreased vertebral BMD. Further studies are necessary to evaluate the clinical importance and pathophysiology of this finding

The NMDA receptor functions independently and as an LRP1 co-receptor to promote Schwann cell survival and migration

NMDA Receptors (NMDA-Rs) are ionotropic glutamate receptors, which associate with LDL Receptor-related Protein-1 (LRP1) to trigger cell-signaling in response to protein ligands in neurons. Herein, we demonstrate for the first time that the NMDA-R is expressed by rat Schwann cells (SCs) and functions independently and with LRP1 to regulate SC physiology. The NR1 and NR2b NMDA-R subunits were expressed by cultured SCs and up-regulated in sciatic nerves following crush injury. The ability of LRP1 ligands to activate ERK1/2 and promote SC migration required the NMDA-R. NR1 gene-silencing compromised SC survival. Injection of the LRP1 ligands, tissue-type plasminogen activator (tPA) or MMP9-PEX, into crush-injured sciatic nerves, activated ERK1/2 in SCs in vivo and the response was blocked by systemic treatment with the NMDA-R inhibitor, MK801. tPA was unique amongst the LRP1 ligands examined because tPA activated cell-signaling and promoted SC migration by interacting with the NMDA-R independently of LRP1, albeit with delayed kinetics. These results define the NMDA-R as a SC signaling receptor for protein ligands and a major regulator of SC physiology, which may be particularly important in PNS injury

Genome-Wide Transposon Screen of a Pseudomonas syringae mexB Mutant Reveals the Substrates of Efflux Transporters.

Bacteria express numerous efflux transporters that confer resistance to diverse toxicants present in their environment. Due to a high level of functional redundancy of these transporters, it is difficult to identify those that are of most importance in conferring resistance to specific compounds. The resistance-nodulation-division (RND) protein family is one such example of redundant transporters that are widespread among Gram-negative bacteria. Within this family, the MexAB-OprM protein complex is highly expressed and conserved among Pseudomonas species. We exposed barcoded transposon mutant libraries in isogenic wild-type and ΔmexB backgrounds in P. syringae B728a to diverse toxic compounds in vitro to identify mutants with increased susceptibility to these compounds. Mutants with mutations in genes encoding both known and novel redundant transporters but with partially overlapping substrate specificities were observed in a ΔmexB background. Psyr_0228, an uncharacterized member of the major facilitator superfamily of transporters, preferentially contributes to tolerance of acridine orange and acriflavine. Another transporter located in the inner membrane, Psyr_0541, contributes to tolerance of acriflavine and berberine. The presence of multiple redundant, genomically encoded efflux transporters appears to enable bacterial strains to tolerate a diversity of environmental toxins. This genome-wide screen performed in a hypersusceptible mutant strain revealed numerous transporters that would otherwise be dispensable under these conditions. Bacterial strains such as P. syringae that likely encounter diverse toxins in their environment, such as in association with many different plant species, probably benefit from possessing multiple redundant transporters that enable versatility with respect to toleration of novel toxicants.IMPORTANCE Bacteria use protein pumps to remove toxic compounds from the cell interior, enabling survival in diverse environments. These protein pumps can be highly redundant, making their targeted examination difficult. In this study, we exposed mutant populations of Pseudomonas syringae to diverse toxicants to identify pumps that contributed to survival in those conditions. In parallel, we examined pump redundancy by testing mutants of a population lacking the primary efflux transporter responsible for toxin tolerance. We identified partial substrate overlap for redundant transporters, as well as several pumps that appeared more substrate specific. For bacteria that are found in diverse environments, having multiple, partially redundant efflux pumps likely allows flexibility in habitat colonization

LDL receptor-related protein-1 regulates NFκB and microRNA-155 in macrophages to control the inflammatory response

LDL receptor-related protein-1 (LRP1) is an endocytic and cell-signaling receptor. In mice in which LRP1 is deleted in myeloid cells, the response to lipopolysaccharide (LPS) was greatly exacerbated. LRP1 deletion in macrophages in vitro, under the control of tamoxifen-activated Cre-ER(T) fusion protein, robustly increased expression of proinflammatory cytokines and chemokines. In LRP1-expressing macrophages, proinflammatory mediator expression was regulated by LRP1 ligands in a ligand-specific manner. The LRP1 agonists, α2-macroglobulin and tissue-type plasminogen activator, attenuated expression of inflammatory mediators, even in the presence of LPS. The antagonists, receptor-associated protein (RAP) and lactoferrin (LF), and LRP1-specific antibody had the entirely opposite effect, promoting inflammatory mediator expression and mimicking LRP1 deletion. NFκB was rapidly activated in response to RAP and LF and responsible for the initial increase in expression of proinflammatory mediators. RAP and LF also significantly increased expression of microRNA-155 (miR-155) after a lag phase of about 4 h. miR-155 expression reflected, at least in part, activation of secondary cell-signaling pathways downstream of TNFα. Although miR-155 was not involved in the initial induction of cytokine expression in response to LRP1 antagonists, miR-155 was essential for sustaining the proinflammatory response. We conclude that LRP1, NFκB, and miR-155 function as members of a previously unidentified system that has the potential to inhibit or sustain inflammation, depending on the continuum of LRP1 ligands present in the macrophage microenvironment

Bridging the physical and virtual with mobile media

This thesis examines how mobile technologies can contribute towards bridging physical and virtual space through interactive, and location-specific, media experiences. Building on a research analysis of contextual discussions and precedents, it is noticeable that there is a discord between physical and virtual space usage as they are often utilised in different situational settings. This thesis therefore develops a mobile application as a wider investigation into how the physical setting and live data can be used to achieve a better link for contextualised content between the physical and virtual in urban areas. It explores this by making a location specific media experience, where the limits of the physical space are incorporated as boundaries in the virtual environment. Further to this, live data is used to influence the dynamics of the environment so that conditions are reflective of the physical world. These investigations are utilised with Augmented Reality, providing an end application that allows the viewer to physically explore urban space within an interactive mobile media experience. This approach offers a new perspective in urban space exploration and mobile media design, highlighting that contextual significance in media experiences are important aspects to consider and design for. Ultimately, such approaches may lead to larger narratives and experiences encompassing entire cities, or other diverse geographies

A unified posterior regularized topic model with maximum margin for learning-to-rank

While most methods for learning-to-rank documents only consider relevance scores as features, better results can often be obtained by taking into account the latent topic structure of the document collection. Existing approaches that consider latent topics follow a two-stage approach, in which topics are discovered in an unsupervised way, as usual, and then used as features for the learning-to-rank task. In contrast, we propose a learning-to-rank framework which integrates the supervised learning of a maximum margin classifier with the discovery of a suitable probabilistic topic model. In this way, the labelled data that is available for the learning-to-rank task can be exploited to identify the most appropriate topics. To this end, we use a unified constrained optimization framework, which can dynamically compute the latent topic similarity score between the query and the document. Our experimental results show a consistent improvement over the state-of-the-art learning-to-rank models