Covariant derivative of the curvature tensor of pseudo-K\"ahlerian manifolds

It is well known that the curvature tensor of a pseudo-Riemannian manifold can be decomposed with respect to the pseudo-orthogonal group into the sum of the Weyl conformal curvature tensor, the traceless part of the Ricci tensor and of the scalar curvature. A similar decomposition with respect to the pseudo-unitary group exists on a pseudo-K\"ahlerian manifold; instead of the Weyl tensor one obtains the Bochner tensor. In the present paper, the known decomposition with respect to the pseudo-orthogonal group of the covariant derivative of the curvature tensor of a pseudo-Riemannian manifold is refined. A decomposition with respect to the pseudo-unitary group of the covariant derivative of the curvature tensor for pseudo-K\"ahlerian manifolds is obtained. This defines natural classes of spaces generalizing locally symmetric spaces and Einstein spaces. It is shown that the values of the covariant derivative of the curvature tensor for a non-locally symmetric pseudo-Riemannian manifold with an irreducible connected holonomy group different from the pseudo-orthogonal and pseudo-unitary groups belong to an irreducible module of the holonomy group.Comment: the final version accepted to Annals of Global Analysis and Geometr

Community characteristics that attract physicians in Japan: a cross-sectional analysis of community demographic and economic factors

<p>Abstract</p> <p>Background</p> <p>In many countries, there is a surplus of physicians in some communities and a shortage in others. Population size is known to be correlated with the number of physicians in a community, and is conventionally considered to represent the power of communities to attract physicians. However, associations between other demographic/economic variables and the number of physicians in a community have not been fully evaluated. This study seeks other parameters that correlate with the physician population and show which characteristics of a community determine its "attractiveness" to physicians.</p> <p>Methods</p> <p>Associations between the number of physicians and selected demographic/economic/life-related variables of all of Japan's 3132 municipalities were examined. In order to exclude the confounding effect of community size, correlations between the physician-to-population ratio and other variable-to-population ratios or variable-to-area ratios were evaluated with simple correlation and multiple regression analyses. The equity of physician distribution against each variable was evaluated by the orenz curve and Gini index.</p> <p>Results</p> <p>Among the 21 variables selected, the service industry workers-to-population ratio (0.543), commercial land price (0.527), sales of goods per person (0.472), and daytime population density (0.451) were better correlated with the physician-to-population ratio than was population density (0.409). Multiple regression analysis showed that the service industry worker-to-population ratio, the daytime population density, and the elderly rate were each independently correlated with the physician-to-population ratio (standardized regression coefficient 0.393, 0.355, 0.089 respectively; each p < 0.001). Equity of physician distribution was higher against service industry population (Gini index = 0.26) and daytime population (0.28) than against population (0.33).</p> <p>Conclusion</p> <p>Daytime population and service industry population in a municipality are better parameters of community attractiveness to physicians than population. Because attractiveness is supposed to consist of medical demand and the amenities of urban life, the two parameters may represent the amount of medical demand and/or the extent of urban amenities of the community more precisely than population does. The conventional demand-supply analysis based solely on population as the demand parameter may overestimate the inequity of the physician distribution among communities.</p

T Cell Integrin Overexpression as a Model of Murine Autoimmunity

Integrin adhesion molecules have important adhesion and signaling functions. They also play a central role in the pathogenesis of many autoimmune diseases. Over the past few years we have described a T cell adoptive transfer model to investigate the role of T cell integrin adhesion molecules in the development of autoimmunity. This report summarizes the methods we used in establishing this murine model. By treating murine CD4+ T cells with DNA hypomethylating agents and by transfection we were able to test the in vitro effects of integrin overexpression on T cell autoreactive proliferation, cytotoxicity, adhesion and trafficking. Furthermore, we showed that the ability to induce in vivo autoimmunity may be unique to the integrin lymphocyte function associated antigen-1 (LFA-1)

Prevalence and socio-demographic correlates for serious injury among adolescents participating in the Djibouti 2007 Global School-based Health Survey

<p>Abstract</p> <p>Background</p> <p>Mental health and injury are neglected public health issues especially in low-income nations. The objective of the study was to determine the prevalence and socio-demographic correlates for serious injury in the last 12 months.</p> <p>Findings</p> <p>The study used data of the 2007 Djibouti Global School-based Health Survey. Logistic regression analysis was used to establish associations. Of the 1, 777 respondents, 61.1% (63.2% males and 57.8% females) reported having sustained serious injury (SSI). Compared to participants who were not bullied, those who reported being bullied 3-9 days per month were more likely to have sustained serious injury in the last 12 months (AOR = 1.27; 95% CI [1.06, 1.52] for 3-5 days of bullying victimization per month, and AOR = 3.19; 95% CI [2.28, 4.47] for 6-9 days per month. Adolescents who were engaged in physical fighting were 47% (AOR = 1.47, 95% CI [1.40, 1.55] more likely to have sustained serious injury compared to those who were not engaged in the fighting. Meanwhile, adolescents who used substances (cigarettes, other forms of tobacco or drugs) were 30% (AOR = 1.30, 95% CI [1.19, 1.42]) more likely to have sustained serious injury compared to those who did not use substances.</p> <p>Conclusions</p> <p>Serious injury is common among adolescents in Djibouti, and we suggest that health workers attending to injured adolescents explore the patients' psycho-social environment. Further, we suggest longitudinal studies where reduction of substance use and bullying may be assessed if they have an impact in reducing serious injury among adolescents.</p

Roles of octopaminergic and dopaminergic neurons in appetitive and aversive memory recall in an insect

<p>Abstract</p> <p>Background</p> <p>In insect classical conditioning, octopamine (the invertebrate counterpart of noradrenaline) or dopamine has been suggested to mediate reinforcing properties of appetitive or aversive unconditioned stimulus, respectively. However, the roles of octopaminergic and dopaminergic neurons in memory recall have remained unclear.</p> <p>Results</p> <p>We studied the roles of octopaminergic and dopaminergic neurons in appetitive and aversive memory recall in olfactory and visual conditioning in crickets. We found that pharmacological blockade of octopamine and dopamine receptors impaired aversive memory recall and appetitive memory recall, respectively, thereby suggesting that activation of octopaminergic and dopaminergic neurons and the resulting release of octopamine and dopamine are needed for appetitive and aversive memory recall, respectively. On the basis of this finding, we propose a new model in which it is assumed that two types of synaptic connections are formed by conditioning and are activated during memory recall, one type being connections from neurons representing conditioned stimulus to neurons inducing conditioned response and the other being connections from neurons representing conditioned stimulus to octopaminergic or dopaminergic neurons representing appetitive or aversive unconditioned stimulus, respectively. The former is called 'stimulus-response connection' and the latter is called 'stimulus-stimulus connection' by theorists studying classical conditioning in higher vertebrates. Our model predicts that pharmacological blockade of octopamine or dopamine receptors during the first stage of second-order conditioning does not impair second-order conditioning, because it impairs the formation of the stimulus-response connection but not the stimulus-stimulus connection. The results of our study with a cross-modal second-order conditioning were in full accordance with this prediction.</p> <p>Conclusion</p> <p>We suggest that insect classical conditioning involves the formation of two kinds of memory traces, which match to stimulus-stimulus connection and stimulus-response connection. This is the first study to suggest that classical conditioning in insects involves, as does classical conditioning in higher vertebrates, the formation of stimulus-stimulus connection and its activation for memory recall, which are often called cognitive processes.</p

Development and evaluation of a new fully automatic motion detection and correction technique in cardiac SPECT imaging

In cardiac SPECT perfusion imaging, motion correction of the data is critical to the minimization of motion introduced artifacts in the reconstructed images. Software-based (data-driven) motion correction techniques are the most convenient and economical approaches to fulfill this purpose. However, the accuracy is significantly affected by how the data complexities, such as activity overlap, non-uniform tissue attenuation, and noise are handled. We developed STASYS, a new, fully automatic technique, for motion detection and correction in cardiac SPECT. We evaluated the performance of STASYS by comparing its effectiveness of motion correcting patient studies with the current industry standard software (Cedars-Sinai MoCo) through blind readings by two readers independently. For 204 patient studies from multiple clinical sites, the first reader identified (1) 69 studies with medium to large axial motion, of which STASYS perfectly or significantly corrected 86.9% and MoCo 72.5%; and (2) 20 studies with medium to large lateral motion, of which STASYS perfectly or significantly corrected 80.0% and MoCo 60.0%. The second reader identified (1) 84 studies with medium to large axial motion, of which STASYS perfectly or significantly corrected 82.2% and MoCo 76.2%; and (2) 34 studies with medium to large lateral motion, of which STASYS perfectly or significantly corrected 58.9% and MoCo 50.0%. We developed a fully automatic software-based motion correction technique, STASYS, for cardiac SPECT. Clinical studies showed that STASYS was effective and corrected a larger percent of cardiac SPECT studies than the current industrial standard software

Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site

The Ubiquitin-Like Protein PLIC-1 or Ubiquilin 1 Inhibits TLR3-Trif Signaling

Background: The innate immune responses to virus infection are initiated by either Toll-like receptors (TLR3/7/8/9) or cytoplasmic double-stranded RNA (dsRNA)-recognizing RNA helicases RIG-I and MDA5. To avoid causing injury to the host, these signaling pathways must be switched off in time by negative regulators. Methodology/Principal Findings: Through yeast-two hybrid screening, we found that an ubiquitin-like protein named protein linking integrin-associated protein to cytoskeleton 1(PLIC-1 or Ubiquilin 1) interacted with the Toll/interleukin-1 receptor (TIR) domain of TLR4. Interestingly, PLIC-1 had modest effect on TLR4-mediated signaling, but strongly suppressed the transcriptional activation of IFN-β promoter through the TLR3-Trif-dependent pathway. Concomitantly, reduction of endogenous PLIC-1 by short-hairpin interfering RNA (shRNA) enhanced TLR3 activation both in luciferase reporter assays as well as in new castle disease virus (NDV) infected cells. An interaction between PLIC-1 and Trif was confirmed in co-immunoprecipitation (Co-IP) and GST-pull-down assays. Subsequent confocal microscopic analysis revealed that PLIC-1 and Trif colocalized with the autophagosome marker LC3 in punctate subcellular structures. Finally, overexpression of PLIC-1 decreased Trif protein abundance in a Nocodazole-sensitive manner. Conclusions: Our results suggest that PLIC-1 is a novel inhibitor of the TLR3-Trif antiviral pathway by reducing the abundance of Trif. © 2011 Biswas et al

Neutrophils Promote Mycobacterial Trehalose Dimycolate-Induced Lung Inflammation via the Mincle Pathway

Trehalose 6,6′-dimycolate (TDM), a cord factor of Mycobacterium tuberculosis (Mtb), is an important regulator of immune responses during Mtb infections. Macrophages recognize TDM through the Mincle receptor and initiate TDM-induced inflammatory responses, leading to lung granuloma formation. Although various immune cells are recruited to lung granulomas, the roles of other immune cells, especially during the initial process of TDM-induced inflammation, are not clear. In this study, Mincle signaling on neutrophils played an important role in TDM-induced lung inflammation by promoting adhesion and innate immune responses. Neutrophils were recruited during the early stage of lung inflammation following TDM-induced granuloma formation. Mincle expression on neutrophils was required for infiltration of TDM-challenged sites in a granuloma model induced by TDM-coated-beads. TDM-induced Mincle signaling on neutrophils increased cell adherence by enhancing F-actin polymerization and CD11b/CD18 surface expression. The TDM-induced effects were dependent on Src, Syk, and MAPK/ERK kinases (MEK). Moreover, coactivation of the Mincle and TLR2 pathways by TDM and Pam3CSK4 treatment synergistically induced CD11b/CD18 surface expression, reactive oxygen species, and TNFα production by neutrophils. These synergistically-enhanced immune responses correlated with the degree of Mincle expression on neutrophil surfaces. The physiological relevance of the Mincle-mediated anti-TDM immune response was confirmed by defective immune responses in Mincle−/− mice upon aerosol infections with Mtb. Mincle-mutant mice had higher inflammation levels and mycobacterial loads than WT mice. Neutrophil depletion with anti-Ly6G antibody caused a reduction in IL-6 and monocyte chemotactic protein-1 expression upon TDM treatment, and reduced levels of immune cell recruitment during the initial stage of infection. These findings suggest a new role of Mincle signaling on neutrophils during anti-mycobacterial responses