CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation

CD40 is a 48-kDa phosphorylated transmembrane glycoprotein belonging to the TNF receptor superfamily. CD40 has been demonstrated on a range of cell types, and it has an important role in adaptive immunity and inflammation. CD40 has recently been described on platelets but platelet activation by CD40 has not been described. In the present study, we use flow cytometry and immunoblotting to confirm that platelets constitutively express surface CD40. CD40 mRNA was undetectable, suggesting that the protein is synthesized early in platelet differentiation by megakaryocytes. Ligation of platelet CD40 with recombinant soluble CD40L trimer (sCD40LT) caused increased platelet CD62P expression, -granule and dense granule release, and the classical morphological changes associated with platelet activation. CD40 ligation also caused ß3 integrin activation, although this was not accompanied by platelet aggregation. These actions were abrogated by the CD40L blocking antibody TRAP-1 and the CD40 blocking antibodies M2 and M3, showing that activation was mediated by CD40L binding to platelet CD40. ß3 integrin blockade with eptifibatide had no effect, indicating that outside-in signaling via IIbß3 was not contributing to these CD40-mediated effects. CD40 ligation led to enhanced platelet-leukocyte adhesion, which is important in the recruitment of leukocytes to sites of thrombosis or inflammation. Our results support a role for CD40-mediated platelet activation in thrombosis, inflammation, and atherosclerosis

Fractal extra dimension in Kaluza-Klein theory

Kaluza-Klein theory in which the geometry of an additional dimension is fractal has been considered. In such a theory the mass of an elementary electric charge appears to be many orders of magnitude smaller than the Planck mass, and the "tower" of masses which correspond to higher integer charges becomes aperiodic.Comment: 3 pages, accepted for publication in Phys.Rev.D (submitted on 3.28.2001

Evolution of replication efficiency following infection with a molecularly cloned feline immunodeficiency virus of low virulence

The development of an effective vaccine against human immunodeficiency virus is considered to be the most practicable means of controlling the advancing global AIDS epidemic. Studies with the domestic cat have demonstrated that vaccinal immunity to infection can be induced against feline immunodeficiency virus (FIV); however, protection is largely restricted to laboratory strains of FIV and does not extend to primary strains of the virus. We compared the pathogenicity of two prototypic vaccine challenge strains of FIV derived from molecular clones; the laboratory strain PET<sub>F14</sub> and the primary strain GL8<sub>414</sub>. PET<sub>F14</sub> established a low viral load and had no effect on CD4<sup>+</sup>- or CD8<sup>+</sup>- lymphocyte subsets. In contrast, GL8<sub>414</sub> established a high viral load and induced a significant reduction in the ratio of CD4<sup>+</sup> to CD8<sup>+</sup> lymphocytes by 15 weeks postinfection, suggesting that PET<sub>F14</sub> may be a low-virulence-challenge virus. However, during long-term monitoring of the PET<sub>F14</sub>-infected cats, we observed the emergence of variant viruses in two of three cats. Concomitant with the appearance of the variant viruses, designated 627<sub>W135</sub> and 628<sub>W135</sub>, we observed an expansion of CD8<sup>+</sup>-lymphocyte subpopulations expressing reduced CD8 ß-chain, a phenotype consistent with activation. The variant viruses both carried mutations that reduced the net charge of the V3 loop (K409Q and K409E), giving rise to a reduced ability of the Env proteins to both induce fusion and to establish productive infection in CXCR4-expressing cells. Further, following subsequent challenge of naïve cats with the mutant viruses, the viruses established higher viral loads and induced more marked alterations in CD8<sup>+</sup>-lymphocyte subpopulations than did the parent F14 strain of virus, suggesting that the E409K mutation in the PET<sub>F14</sub> strain contributes to the attenuation of the virus

Efficacy and tolerability of the Galanin Analog NAX 5055 in the multiple-hit rat model of symptomatic infantile spasms

Infantile spasms are seizures manifesting in infantile epileptic encephalopathies that are associated with poor epilepsy and cognitive outcomes. The current therapies are not always effective or are associated with serious side effects. Early cessation of spasms has been proposed to improve long-term outcomes. To identify new therapies for infantile spasms with rapid suppression of spasms, we are using the multiple-hit rat model of infantile spasms, which is a model of refractory infantile spasms. Here, we are testing the efficacy and tolerability of a single dose of the galanin receptor 1 preferring analog, NAX 5055, in the multiple-hit model of spasms. To induce the model, postnatal day 3 (PN3) male Sprague-Dawley rats underwent right intracerebral infusions of doxorubicin and lipopolysaccharide; p-chlorophenylalanine was then injected intraperitoneally (i.p.) at PN5. After the onset of spasms at PN4, 11-14 rats/group were injected i.p. with either NAX 5055 (0.5, 1, 2, or 4mg/kg) or vehicle. Video monitoring for spasms included a 1h pre-injection period, followed by 5h of recording post-injection, and two 2h sessions on PN5. The study was conducted in a randomized, blinded manner. Neurodevelopmental reflexes were assessed daily as well as at 2h after injection. Respiratory function, heart rate, pulse distension, oximetry and blood glucose were measured 4h after injection. The relative expression of GalR1 and GalR2 mRNA over β-actin in the cerebral cortex and hippocampus was determined with real time reverse transcription polymerase chain reaction. There was no acute effect of NAX 5055 on spasm frequency after the single dose of NAX 5055 (n=11-13 rats/group, following exclusions). Neurodevelopmental reflexes, vital signs, blood glucose measured 4h post-injection, and survival were not affected. A reduction in pulse and breath distention of unclear clinical significance was observed with the 7mg/kg NAX 5055 dose. GalR1 mRNA was present in the cerebral cortex and hippocampus of PN4 and adult rats. The hippocampal - but not the cortical - GalR1 mRNA expression was significantly lower in PN4 pups than in adults. GalR1 mRNA was also at least 20 times less abundant in the PN4 cortex than GalR2 mRNA. In conclusion, a single dose of NAX 5055 has no acute efficacy on spasms or toxicity in the multiple hit rat model of medically refractory infantile spasms. Our findings cannot exclude the possibility that repetitive NAX 5055 administration may show efficacy on spasms. The higher expression of GalR2 in the PN4 cortex suggests that GalR2-preferring analogs may be of interest to test for efficacy on spasms

Data Analysis Techniques, Differential Cross Sections, and Spin Density Matrix Elements for the Reaction ᵞp → ϕp

High-statistics measurements of differential cross sections and spin density matrix elements for the reaction ᵞp → ϕp have been made using the CLAS detector at Jefferson Lab. We cover center-of-mass energies (√s) from 1.97 to 2.84 GeV, with an extensive coverage in the ϕ production angle. The high statistics of the data sample made it necessary to carefully account for the interplay between the ϕ natural lineshape and effects of the detector resolution, that are found to be comparable in magnitude. We study both the charged-(ϕ → K+ K-) and neutral( ϕ → (KOSKOL) K K- decay modes of the ϕ. Further, for the charged mode, we differentiate between the cases where the final K-is directly detected or its momentum reconstructed as the total missing momentum in the event. The two charged-mode topologies and the neutral-mode have different resolutions and are calibrated against each other. Extensive usage is made of kinematic fitting to improve the reconstructed ϕ mass resolution. Our final results are reported in 10- and mostly 30-MeV-wide √s bins for the charged-and the neutral-modes, respectively. Possible effects from K+Λ* channels with p K K- final states are discussed. These present results constitute the most precise and extensive ϕ photoproduction measurements to date and in conjunction with the ω photoproduction results recently published by CLAS, will greatly improve our understanding of low energy vector meson photoproduction

Contexts of diffusion: Adoption of research synthesis in Social Work and Women's Studies

Texts reveal the subjects of interest in research fields, and the values, beliefs, and practices of researchers. In this study, texts are examined through bibliometric mapping and topic modeling to provide a birds eye view of the social dynamics associated with the diffusion of research synthesis methods in the contexts of Social Work and Women's Studies. Research synthesis texts are especially revealing because the methods, which include meta-analysis and systematic review, are reliant on the availability of past research and data, sometimes idealized as objective, egalitarian approaches to research evaluation, fundamentally tied to past research practices, and performed with the goal informing future research and practice. This study highlights the co-influence of past and subsequent research within research fields; illustrates dynamics of the diffusion process; and provides insight into the cultural contexts of research in Social Work and Women's Studies. This study suggests the potential to further develop bibliometric mapping and topic modeling techniques to inform research problem selection and resource allocation.Comment: To appear in proceedings of the 2014 International Conference on Social Computing, Behavioral-Cultural Modeling, and Prediction (SBP2014

Poincar\'{e} cycle of a multibox Ehrenfest urn model with directed transport

We propose a generalized Ehrenfest urn model of many urns arranged periodically along a circle. The evolution of the urn model system is governed by a directed stochastic operation. Method for solving an $N$-ball, $M$-urn problem of this model is presented. The evolution of the system is studied in detail. We find that the average number of balls in a certain urn oscillates several times before it reaches a stationary value. This behavior seems to be a peculiar feature of this directed urn model. We also calculate the Poincar\'{e} cycle, i.e., the average time interval required for the system to return to its initial configuration. The result can be easily understood by counting the total number of all possible microstates of the system.Comment: 10 pages revtex file with 7 eps figure

Electric/Magnetic Duality with Gauge Singlets

We demonstrate how gauge singlets can be used to find new examples of Kutasov duality (i.e. where the matching of the dual theories relies on a non-zero superpotential) in N}=1 SU(N) SQCD with F_Q flavours of quark and multiple generations of adjoints, or antisymmetrics, or symmetrics. The role of the singlets is to simplify greatly the truncation of the chiral ring whilst maintaining an R-symmetry, and at the same time allowing an unambiguous identification of the elementary mesons of the magnetic theory. The dual theories satisfy all the usual tests, including the highly non-trivial 't Hooft anomaly matching conditions.Comment: 31 pages, 2 figure

Relativistic effects and quasipotential equations

We compare the scattering amplitude resulting from the several quasipotential equations for scalar particles. We consider the Blankenbecler-Sugar, Spectator, Thompson, Erkelenz-Holinde and Equal-Time equations, which were solved numerically without decomposition into partial waves. We analyze both negative-energy state components of the propagators and retardation effects. We found that the scattering solutions of the Spectator and the Equal-Time equations are very close to the nonrelativistic solution even at high energies. The overall relativistic effect increases with the energy. The width of the band for the relative uncertainty in the real part of the scattering $T$ matrix, due to different dynamical equations, is largest for backward-scattering angles where it can be as large as 40%.Comment: Accepted for publication in Phys. Rev.