Forging a potent vaccine adjuvant: CpG ODN/cationic peptide nanorings

Cataloged from PDF version of article.Type I interferon inducers may potentially be engineered to function as antiviral and anticancer agents, or alternatively, vaccine adjuvants, all of which may have clinical applications. We recently described a simple strategy to convert a Toll-like receptor 9 (TLR9) agonist devoid of interferon alpha (IFN alpha) stimulating activity into a robust Type I interferon inducer with potent vaccine adjuvant activity

Immunostimulatory activity of polysaccharide-poly(I:C) nanoparticles

Cataloged from PDF version of article.Immunostimulatory properties of mushroom derived polysaccharides (PS) as stand-alone agents were tested. Next. PS were nanocomplexed with polyI:C (pIC) to yield stable nanoparticles around 200 nm in size evidenced by atomic force microscopy and dynamic light scattering analyses. PSs were selectively engaged by cells expressing TLR2 and initiated NF kappa B dependent signaling cascade leading to a Th1-biased cytokine/chemokine secretion in addition to bactericidal nitric oxide (NO) production from macrophages. Moreover, cells treated with nanoparticles led to synergistic IL6, production and upregulation of TNF alpha, MIP3 alpha, IFN gamma and IP10 transcript expression. In mice, PS-Ovalbumin-pIC formulation surpassed anti-OVA IgG responses when compared to either PS-OVA or pIC-OVA mediated immunity. Our results revealed that signal transduction initiated both by TLR2 and TLR3 via co-delivery of pIC by PS in nanoparticle depot delivery system is an effective immunization strategy. The present work implicate that the PS and nucleic acid based nanoparticle approach along with protein antigens can be harnessed to prevent infectious diseases. (C) 2011 Elsevier Ltd. All rights reserve

The effects of an insertion in the 5 ' UTR of the AMCase on gene expression and pulmonary functions

Cataloged from PDF version of article.Background: Studies regarding the physiological role of acidic mammalian chitinase (AMCase) and the effects of its genetic variants on asthma have produced conflicting results. Objectives: We aimed to determine the genetic variants in the AMCase gene that could regulate the gene expression and thus influence disease severity. Methods: Genetic variants of the AMCase gene were determined by sequencing of asthmatics and healthy controls in up to -1 kb in the promoter region and exon 1 and 2. In an association study, a population of asthmatic (n = 504) and healthy Turkish children (n = 188) were genotyped for the observed SNPs. A replication study was performed in a North American adult population of patients with mild (n = 317) and severe (n = 145) asthma. The functional properties of the insertion were determined by promoter reporter assay, electromobility shift assay and transcription factor ELISA experiments. Results: Of the identified SNPs, only a ten base pair insertion (CAATCTAGGC) in the 5'UTR region of exon 2 was significantly associated with lower FEV(1) (beta = -14.63 SE = 6.241, P = 0.019) in Turkish children with asthma. However, in the adult population, the same insertion showed a trend toward higher FEV(1). The insertion was shown to have enhancer activity and the mutant probe possessing the insertion had higher binding affinity for the nuclear extracts. Conclusion: Our study shows that a ten base pair insertion in the 5'UTR region of AMCase gene may modify gene expression and thus may affect the severity of asthma. However, its effects appear to be different in different populations. (C) 2011 Elsevier Ltd. All rights reserved

Renormalization of the charged scalar field in curved space

The DeWitt-Schwinger proper time point-splitting procedure is applied to a massive complex scalar field with arbitrary curvature coupling interacting with a classical electromagnetic field in a general curved spacetime. The scalar field current is found to have a linear divergence. The presence of the external background gauge field is found to modify the stress-energy tensor results of Christensen for the neutral scalar field by adding terms of the form $(eF)^2$ to the logarithmic counterterms. These results are shown to be expected from an analysis of the degree of divergence of scalar quantum electrodynamics.Comment: 24 pages REVTe

Circulating LL37 targets plasma extracellular vesicles to immune cells and intensifies Behçet's disease severity

Behçet's disease (BD) activity is characterised by sustained, over-exuberant immune activation, yet the underlying mechanisms leading to active BD state are poorly defined. Herein, we show that the human cathelicidin derived antimicrobial peptide LL37 associates with and directs plasma extracellular vesicles (EV) to immune cells, thereby leading to enhanced immune activation aggravating BD pathology. Notably, disease activity was correlated with elevated levels of circulating LL37 and EV plasma concentration. Stimulation of healthy PBMC with active BD patient EVs induced heightened IL1β, IFNα, IL6 and IP10 secretion compared to healthy and inactive BD EVs. Remarkably, when mixed with LL37, healthy plasma-EVs triggered a robust immune activation replicating the pathology inducing properties of BD EVs. The findings of this study could be of clinical interest in the management of BD, implicating LL37/EV association as one of the major contributors of BD pathogenesis. © 2017 The Author(s)

Fundamental Physics with the Laser Astrometric Test Of Relativity

The Laser Astrometric Test Of Relativity (LATOR) is a joint European-U.S. Michelson-Morley-type experiment designed to test the pure tensor metric nature of gravitation - a fundamental postulate of Einstein's theory of general relativity. By using a combination of independent time-series of highly accurate gravitational deflection of light in the immediate proximity to the Sun, along with measurements of the Shapiro time delay on interplanetary scales (to a precision respectively better than 0.1 picoradians and 1 cm), LATOR will significantly improve our knowledge of relativistic gravity. The primary mission objective is to i) measure the key post-Newtonian Eddington parameter \gamma with accuracy of a part in 10^9. (1-\gamma) is a direct measure for presence of a new interaction in gravitational theory, and, in its search, LATOR goes a factor 30,000 beyond the present best result, Cassini's 2003 test. The mission will also provide: ii) first measurement of gravity's non-linear effects on light to ~0.01% accuracy; including both the Eddington \beta parameter and also the spatial metric's 2nd order potential contribution (never measured before); iii) direct measurement of the solar quadrupole moment J2 (currently unavailable) to accuracy of a part in 200 of its expected size; iv) direct measurement of the "frame-dragging" effect on light by the Sun's gravitomagnetic field, to 1% accuracy. LATOR's primary measurement pushes to unprecedented accuracy the search for cosmologically relevant scalar-tensor theories of gravity by looking for a remnant scalar field in today's solar system. We discuss the mission design of this proposed experiment.Comment: 8 pages, 9 figures; invited talk given at the 2005 ESLAB Symposium "Trends in Space Science and Cosmic Vision 2020," 19-21 April 2005, ESTEC, Noodrwijk, The Netherland

Internal Structure of Einstein-Yang-Mills Black Holes

It is shown that a generic black hole solution of the SU(2) Einstein-Yang-Mills equations develops a new type of an infinitely oscillating behavior near the singularity. Only for certain discrete values of the event horizon radius exceptional solutions exist, possessing an inner structure of the Schwarzschild or Reissner-Nordstrom type.Comment: 4.5 LaTeX pages, 8 eps figures, uses RevTeX, boxedeps.tex. 4 more typos fixed, a footnote adde

The late-time singularity inside non-spherical black holes

It was long believed that the singularity inside a realistic, rotating black hole must be spacelike. However, studies of the internal geometry of black holes indicate a more complicated structure is typical. While it seems likely that an observer falling into a black hole with the collapsing star encounters a crushing spacelike singularity, an observer falling in at late times generally reaches a null singularity which is vastly different in character to the standard Belinsky, Khalatnikov and Lifschitz (BKL) spacelike singularity. In the spirit of the classic work of BKL we present an asymptotic analysis of the null singularity inside a realistic black hole. Motivated by current understanding of spherical models, we argue that the Einstein equations reduce to a simple form in the neighborhood of the null singularity. The main results arising from this approach are demonstrated using an almost plane symmetric model. The analysis shows that the null singularity results from the blueshift of the late-time gravitational wave tail; the amplitude of these gravitational waves is taken to decay as an inverse power of advanced time as suggested by perturbation theory. The divergence of the Weyl curvature at the null singularity is dominated by the propagating modes of the gravitational field. The null singularity is weak in the sense that tidal distortion remains bounded along timelike geodesics crossing the Cauchy horizon. These results are in agreement with previous analyses of black hole interiors. We briefly discuss some outstanding problems which must be resolved before the picture of the generic black hole interior is complete.Comment: 16 pages, RevTeX, 3 figures included using psfi

A report on the piloting of a novel computer-based medical case simulation for teaching and formative assessment of diagnostic laboratory testing

Objectives: Insufficient attention has been given to how information from computer-based clinical case simulations is presented, collected, and scored. Research is needed on how best to design such simulations to acquire valid performance assessment data that can act as useful feedback for educational applications. This report describes a study of a new simulation format with design features aimed at improving both its formative assessment feedback and educational function. Methods: Case simulation software (LabCAPS) was developed to target a highly focused and well-defined measurement goal with a response format that allowed objective scoring. Data from an eight-case computer-based performance assessment administered in a pilot study to 13 second-year medical students was analyzed using classical test theory and generalizability analysis. In addition, a similar analysis was conducted on an administration in a less controlled setting, but to a much large sample (n=143), within a clinical course that utilized two random case subsets from a library of 18 cases. Results: Classical test theory case-level item analysis of the pilot assessment yielded an average case discrimination of 0.37, and all eight cases were positively discriminating (range=0.11–0.56). Classical test theory coefficient alpha and the decision study showed the eight-case performance assessment to have an observed reliability of σ=G=0.70. The decision study further demonstrated that a G=0.80 could be attained with approximately 3 h and 15 min of testing. The less-controlled educational application within a large medical class produced a somewhat lower reliability for eight cases (G=0.53). Students gave high ratings to the logic of the simulation interface, its educational value, and to the fidelity of the tasks. Conclusions: LabCAPS software shows the potential to provide formative assessment of medical students’ skill at diagnostic test ordering and to provide valid feedback to learners. The perceived fidelity of the performance tasks and the statistical reliability findings support the validity of using the automated scores for formative assessment and learning. LabCAPS cases appear well designed for use as a scored assignment, for stimulating discussions in small group educational settings, for self-assessment, and for independent learning. Extension of the more highly controlled pilot assessment study with a larger sample will be needed to confirm its reliability in other assessment applications

The Palomar Testbed Interferometer

The Palomar Testbed Interferometer (PTI) is a long-baseline infrared interferometer located at Palomar Observatory, California. It was built as a testbed for interferometric techniques applicable to the Keck Interferometer. First fringes were obtained in July 1995. PTI implements a dual-star architecture, tracking two stars simultaneously for phase referencing and narrow-angle astrometry. The three fixed 40-cm apertures can be combined pair-wise to provide baselines to 110 m. The interferometer actively tracks the white-light fringe using an array detector at 2.2 um and active delay lines with a range of +/- 38 m. Laser metrology of the delay lines allows for servo control, and laser metrology of the complete optical path enables narrow-angle astrometric measurements. The instrument is highly automated, using a multiprocessing computer system for instrument control and sequencing.Comment: ApJ in Press (Jan 99) Fig 1 available from http://huey.jpl.nasa.gov/~bode/ptiPicture.html, revised duging copy edi