Adjuvants : an essential component of neisseria vaccines

Adjuvants may be classified into delivery systems and immune potentiator or modulator molecules based on their mechanism of action. Neisseria vaccines containing traditional adjuvants such as aluminium salts have existed for long time, but meningitis caused by Neisseria meningitidis serogroups, particularly serogroup B, continues to be a global health problem. Novel strategies have applied in silico and recombinant technologies to develop "universal" antigens (e.g. proteins, peptides and plasmid DNA) for vaccines, but these antigens have been shown to be poorly immunogenic even when alum adjuvanted, implying a need for better vaccine design. In this work we review the use of natural, detoxified, or synthetic molecules in combination with antigens to activate the innate immune system and to modulate the adaptive immune responses. In the main, antigenic and imune potentiator signals are delivered using nano-, micro-particles, alum, or emulsions. The importance of interaction between adjuvants and antigens to activate and target dendritic cells, the bridge between the innate and adaptive immune systems, will be discussed. In addition, nasal vaccine strategies based on the development of mucosal adjuvants and Neisseria derivatives to eliminate the pathogen at the site of infection provide promising adjuvants effective not only against respiratory pathogens, but also against pathogens responsible for enteric and sexually transmitted diseases

Defining the natural history of rare genetic liver diseases:Lessons learned from the NAPPED initiative

While rare diseases collectively affect similar to 300 million people worldwide, the prevalence of each disease concerns a relatively small number of patients. Usually, only limited data with regard to natural history are available. Multicenter initiatives are needed to aggregate data and answer clinically relevant research questions. In 2017, we launched the NAtural course and Prognosis of PFIC and Effect of biliary Diversion (NAPPED) consortium. In three years, NAPPED created a global network focused on rare genetic liver diseases in the Progressive Familial Intrahepatic Cholestasis (PFIC) spectrum. During these years, we have learned important lessons which we feel should be taken into account when initiating and leading a global consortium.First, it is essential to 'keep it simple' from the start. Research questions, case report forms (CRFs) and data acquisition should be limited and clear to stay focused and keep the workload low for new participants. Secondly, early rewards and research output are needed to keep momentum and motivation. Quick output can only follow a clean and simple design. Thirdly, the leading team should be in touch and accessible. Ideally, an involved PhD-candidate is appointed as primary contact person. Lastly, be inclusive and actively involve all participants the consortium's course.Global consortia are critical for personalized medicine in rare diseases. Also, they are essential for setting up trials to investigate generic drugs and personalized therapies. We hope to herewith stimulate others that are starting (or are planning to start) a global consortium, ultimately to help improve the care for patients with a rare disease.</p

Exploration Of The Relationship Between LMX And Demographic Variables

This study of 143 participants from an international company examined the relationship between LMX and demographic variables. LMX results represent the quality of the dyadic relationship between leader and follower. Demographic variables included age, gender, education and organizational tenure. Study results suggest significant findings between education and LMX results at the follower level

A Comparison of Spectroscopic versus Imaging Techniques for Detecting Close Companions to Kepler Objects of Interest

(Abbreviated) Kepler planet candidates require both spectroscopic and imaging follow-up observations to rule out false positives and detect blended stars. [...] In this paper, we examine a sample of 11 Kepler host stars with companions detected by two techniques -- near-infrared adaptive optics and/or optical speckle interferometry imaging, and a new spectroscopic deblending method. We compare the companion Teff and flux ratios (F_B/F_A, where A is the primary and B is the companion) derived from each technique, and find no cases where both companion parameters agree within 1sigma errors. In 3/11 cases the companion Teff values agree within 1sigma errors, and in 2/11 cases the companion F_B/F_A values agree within 1sigma errors. Examining each Kepler system individually considering multiple avenues (isochrone mapping, contrast curves, probability of being bound), we suggest two cases for which the techniques most likely agree in their companion detections (detect the same companion star). Overall, our results support the advantage the spectroscopic deblending technique has for finding very close-in companions ($\theta \lesssim$0.02-0.05") that are not easily detectable with imaging. However, we also specifically show how high-contrast AO and speckle imaging observations detect companions at larger separations ($\theta \geq$0.02-0.05") that are missed by the spectroscopic technique, provide additional information for characterizing the companion and its potential contamination (e.g., PA, separation, $\Delta$m), and cover a wider range of primary star effective temperatures. The investigation presented here illustrates the utility of combining the two techniques to reveal higher-order multiples in known planet-hosting systems.Comment: Accepted to AJ. 40 pages, 12 figure

Discovery of a redshift 6.13 quasar in the UKIRT infrared deep sky survey

Original article can be found at: http://www.aanda.org/ Copyright The European Southern Observatory (ESO) DOI: 10.1051/0004-6361/200811161Optical and near-infrared (NIR) spectra are presented for ULAS J131911.29+095051.4 (hereafter ULAS J1319+0950), a new redshift z = 6.127 0.004 quasar discovered in the Third Data Release (DR3) of the UKIRT Infrared Deep Sky Survey (UKIDSS). The source has = 19.10 0.03, corresponding to = -27.12, which is comparable to the absolute magnitudes of the z 6 quasars discovered in the Sloan Digital Sky Survey (SDSS). ULAS J1319+0950 was, in fact, registered by SDSS as a faint source with = 20.13 0.12, just below the signal-to-noise ratio limit of the SDSS high-redshift quasar survey. The faint z-band magnitude is a consequence of the weak Ly /N V emission line, which has a rest-frame equivalent width of ~20Å and provides only a small boost to the z-band flux. Nevertheless, there is no evidence of a significant new population of high-redshift quasars with weak emission lines from this UKIDSS-based search. The Ly  optical depth to ULAS J1319+0950 is consistent with that measured towards similarly distant SDSS quasars, implying that results from optical- and NIR-selected quasars may be combined in studies of cosmological reionization. Also presented is a new NIR-spectrum of the previously discovered UKIDSS quasar ULAS J020332.38+001229.2, which reveals the object to be a broad absorption line quasar. The new spectrum shows that the emission line initially identified as Ly  is actually N V, leading to a revised redshift of z = 5.72, rather than z = 5.86 as previously estimatedPeer reviewe

Binding of Antitumor Ruthenium(III) Complexes to Plasma Proteins

Presently, there is large interest in analysing the interactions in vitro with plasma proteins of some novel antitumor ruthenium(III) complexes that are in preclinical or clinical phase. The joint application of separation and spectroscopic techniques provides valuable information on the nature and the properties of the resulting ruthenium/protein adducts. Recent work carried out in our laboratory points out that, under physiological conditions, some selected ruthenium(III) complexes bind plasma proteins tightly with a marked preference for surface imidazole groups. Representative examples of interactions of antitumor ruthenium(III) complexes with plasma proteins such as albumin and transferrin are given. Notably the antitumor ruthenium(III) complexes considered here bind proteins much tighter than DNA; it is proposed that protein binding of ruthenium(III) complexes will have a large impact on the biodistribution, the pharmacokinetics and the mechanism of action of these experimental drugs

Hard Thermal Loops, Static Response and the Composite Effective Action

First, we investigate the static non-Abelian Kubo equation. We prove that it does not possess finite energy solutions; thereby we establish that gauge theories do not support hard thermal solitons. A similar argument shows that "static" instantons are absent. In addition, we note that the static equations reproduce the expected screening of the non-Abelian electric field by a gauge invariant Debye mass m=gT sqrt((N+N_F/2)/3). Second, we derive the non-Abelian Kubo equation from the composite effective action. This is achieved by showing that the requirement of stationarity of the composite effective action is equivalent, within a kinematical approximation scheme, to the condition of gauge invariance for the generating functional of hard thermal loops.Comment: 17 pages, MIT preprint CTP#2261. An Appendix [including one (appended) PS figure] presenting a numerical analysis of the static solutions has been included. A note relating our approach to alternative ones has been added. We have also added references and comments in Section II

Chaplygin gas with non-adiabatic pressure perturbations

Perturbations in a Chaplygin gas, characterized by an equation of state $p = -A/\rho$, may acquire non-adiabatic contributions if spatial variations of the parameter $A$ are admitted. This feature is shown to be related to a specific internal structure of the Chaplygin gas. We investigate how perturbations of this type modify the adiabatic sound speed and influence the time dependence of the gravitational potential which gives rise to the Integrated Sachs-Wolfe effect in the anisotropy spectrum of the cosmic microwave background.Comment: 16 pages, comments and references added, accepted for publication in Class.Quantum Gra

FREEZE/THAW IMPACTS ON RADON DIFFUSION CHARACTERISTICS OF COVER SOIL ON THE UMTRA PROJECT

ABSTRACT A simple study was performed to access the effects of freeze/thaw cycles on radon diffusion coefficients for unsaturated cover soil used to environmentally isolate uranium mill tailings on the Uranium Mill Tailings Remedial Action (UMTRA) Project. Typical radon barrier soil (Estes Gultch barrow source, Rifle, CO) was compacted to 95-percent Proctor in a 4-inch high, 4-inch diameter cylindrical steel mold used to perform standard transient radon diffusion coefficient measurements. Samples were prepared at 4.4, 9.4, and 13.7 percent by weight moisture content, corresponding to 22, 46, and 68 percent moisture saturation, respectively. The compacted, moisture conditioned soil samples were sealed in the molds by spring-loaded steel plates, and the samples were subjected to 13 rapid freeze/thaw cycles using the freezer compartment of a conventional, domestic refrigerator: 15 hours freezing followed by 9 hours thawing. In the process, soil temperatures cycled between -12 and 20 degrees centigrade. After 13 cycles, the diffusion coefficient for each sample was measured using the transient diffusion method and compared to corresponding measurements made prior to initiating the cyclical freeze/thaw treatment. The results of this freeze/thaw experiment indicate that the freeze/thaw cycling of typical radon barrier soil, with moisture saturation less than 75 percent, would not significantly alter the radon diffusion properties of the cover soil. The relationship of these findings to observations noted by others and their application to the UMTRA Project is discussed