Latent Membrane Protein 1 as a molecular adjuvant for single-cycle lentiviral vaccines

Background Molecular adjuvants are a promising method to enhance virus-specific immune responses and protect against HIV-1 infection. Immune activation by ligands for receptors such as CD40 can induce dendritic cell activation and maturation. Here we explore the incorporation of two CD40 mimics, Epstein Barr Virus gene LMP1 or an LMP1-CD40 chimera, into a strain of SIV that was engineered to be limited to a single cycle of infection. Results Full length LMP1 or the chimeric protein LMP1-CD40 was cloned into the nef-locus of single-cycle SIV. Human and Macaque monocyte derived macrophages and DC were infected with these viruses. Infected cells were analyzed for activation surface markers by flow cytometry. Cells were also analyzed for secretion of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12p70 and TNF by cytometric bead array. Conclusions Overall, single-cycle SIV expressing LMP1 and LMP1-CD40 produced a broad and potent T$_H$1-biased immune response in human as well as rhesus macaque macrophages and DC when compared with control virus. Single-cycle SIV-LMP1 also enhanced antigen presentation by lentiviral vector vaccines, suggesting that LMP1-mediated immune activation may enhance lentiviral vector vaccines against HIV-1

Influence of interfacial gas enrichment on controlled coalescence of oil droplets in water in microfluidics

Interfacial gas enrichment (IGE) of dissolved gases in water is shown to govern the strong attraction between solid hydrophobic surfaces of an atomic force microscopy (AFM) colloidal probe and a solid substrate. However, the role of IGE in controlling the attraction between fluid-fluid interfaces of foam films and emulsion films is difficult to establish by AFM techniques due to the extremely fast coalescence. Here, we applied droplet-based microfluidics to capture the fast coalescence event under the creeping flow condition and quantify the effect of IGE on the drainage and stability of water films between coalescing oil droplets. The amount of dissolved gases is controlled by partially degassing the oil phase. When the amount of dissolved gases (oxygen) in oil decreases (from 7.89 mg/L to 4.59 mg/L), the average drainage time of coalescence significantly increases (from 19 ms to 50 ms). Our theoretical quantification of the coalescence by incorporating IGE into the multilayer van der Waals attraction theory confirms the acceleration of film drainage dynamics by the van der Waals attractive force generated by IGE. The thickness of the IGE layer decreases from 5.5 nm to 4.9 nm when the amount of dissolved gas decreases from 7.89 mg/L to 4.59 mg/L. All these results establish the universal role of dissolved gases in governing the strong attraction between particulate hydrophobic interfaces

The reductive activation of CO2 across a Ti═Ti double bond: synthetic, structural, and mechanistic studies

[Image: see text] The reactivity of the bis(pentalene)dititanium double-sandwich compound Ti(2)Pn(†)(2) (1) (Pn(†) = 1,4-{Si(i)Pr(3)}(2)C(8)H(4)) with CO(2) is investigated in detail using spectroscopic, X-ray crystallographic, and computational studies. When the CO(2) reaction is performed at −78 °C, the 1:1 adduct 4 is formed, and low-temperature spectroscopic measurements are consistent with a CO(2) molecule bound symmetrically to the two Ti centers in a μ:η(2),η(2) binding mode, a structure also indicated by theory. Upon warming to room temperature the coordinated CO(2) is quantitatively reduced over a period of minutes to give the bis(oxo)-bridged dimer 2 and the dicarbonyl complex 3. In situ NMR studies indicated that this decomposition proceeds in a stepwise process via monooxo (5) and monocarbonyl (7) double-sandwich complexes, which have been independently synthesized and structurally characterized. 5 is thermally unstable with respect to a μ-O dimer in which the Ti–Ti bond has been cleaved and one pentalene ligand binds in an η(8) fashion to each of the formally Ti(III) centers. The molecular structure of 7 shows a “side-on” bound carbonyl ligand. Bonding of the double-sandwich species Ti(2)Pn(2) (Pn = C(8)H(6)) to other fragments has been investigated by density functional theory calculations and fragment analysis, providing insight into the CO(2) reaction pathway consistent with the experimentally observed intermediates. A key step in the proposed mechanism is disproportionation of a mono(oxo) di-Ti(III) species to yield di-Ti(II) and di-Ti(IV) products. 1 forms a structurally characterized, thermally stable CS(2) adduct 8 that shows symmetrical binding to the Ti(2) unit and supports the formulation of 4. The reaction of 1 with COS forms a thermally unstable complex 9 that undergoes scission to give mono(μ-S) mono(CO) species 10. Ph(3)PS is an effective sulfur transfer agent for 1, enabling the synthesis of mono(μ-S) complex 11 with a double-sandwich structure and bis(μ-S) dimer 12 in which the Ti–Ti bond has been cleaved

What are the hot R Coronae Borealis stars?

We investigate the evolutionary status of four stars: V348 Sgr, DY Cen, and MV Sgr in the Galaxy and HV 2671 in the LMC. These stars have in common random deep declines in visual brightness, which are characteristic of R Coronae Borealis (RCB) stars. RCB stars are typically cool hydrogen-deficient supergiants. The four stars studied in this paper are hotter (Teff = 15–20 kK) than the majority of RCB stars (Teff = 5000–7000 K). Although these are commonly grouped together as the hot RCB stars they do not necessarily share a common evolutionary history. We present new observational data and an extensive collection of archival and previously published data that is reassessed to ensure internal consistency. We find temporal variations of various properties on different timescales that will eventually help us to uncover the evolutionary history of these objects. DY Cen and MV Sgr have typical RCB helium abundances, which exclude any currently known post–asymptotic giant branch (post-AGB) evolutionary models. Moreover, their carbon and nitrogen abundances present us with further problems for their interpretation. V348 Sgr and HV 2671 are in general agreement with a born-again post-AGB evolution, and their abundances are similar to Wolf-Rayet central stars of planetary nebulae (PNs). The three Galactic stars in the sample have circumstellar nebulae, which produce forbidden line radiation (for HV 2671 we have no information). V348 Sgr and DY Cen have low-density, low-expansion velocity nebulae (resolved in the case of V348 Sgr), while MV Sgr has a higher density, higher expansion velocity nebula. All three stars, on the other hand, have split emission lines, which indicate the presence of an equatorial bulge but not of a Keplerian disk. In addition, the historical light curves for the three Galactic hot RCB stars show evidence for a significant fading in their maximum-light brightnesses of ~1 mag over the last 70 yr. From this we deduce that their effective temperatures increased by a few thousand degrees. If V348 Sgr is a born-again star, as we presume, this means that the star is returning from the born-again AGB phase to the phase of a central star of PN. Spectroscopically, no dramatic change is observed over the last 50 years for V348 Sgr and MV Sgr. However, there is some evidence that the winds of V348 Sgr and DY Cen have increased in strength in the last decade. HV 2671, located in the LMC, has not been analyzed in detail but at 5 Å… resolution is almost identical to V348 Sgr. Through the bolometric correction derived for V348 Sgr and the known distance, we can estimate the absolute ν magnitude of HV 2671 (Mν = -3.0 mag) and its bolometric luminosity (~6000 L⊙)

Effect of a cluster on gas–solid drag from lattice Boltzmann simulations

Fast fluidization of fine particles leads to formation of particle clusters, which significantly affects the drag force between the phases. Existing gas–solid drag models, both empirical and theoretical, do not account for the effect of the clusters on the drag force, and as a result, the computational studies using them are unable to capture the inherent heterogeneity of fast fluidization beds. The limitation of the current drag models is generally attributed to poor understanding of the effect of the clusters. In this study, the effect of a single cluster on the drag force has been investigated by conducting lattice Boltzmann simulations of gas–particle flow under a wide range of the overall voidage and particle Reynolds numbers. It was observed that simulations with the particles in a cluster configuration gave considerably lower drag than those with particles in a random arrangement. Furthermore, for the cluster voidage between maximum to 0.7, a significant drag reduction was observed when the inter-particle distances within a cluster was decreased. The simulations with a constant cluster voidage of 0.7 showed that the drag force decreased on decreasing the overall voidage from the maximum voidage to approximately 0.96; however any further decrease in the overall voidage caused a steep increase in the drag force. The results of this study are important in quantifying the drag reduction due to the formation of clusters

High-resolution in situ observations of electron precipitation-causing EMIC waves

Electromagnetic ion cyclotron (EMIC) waves are thought to be important drivers of energetic electron losses from the outer radiation belt through precipitation into the atmosphere. While the theoretical possibility of pitch angle scattering-driven losses from these waves has been recognized for more than four decades, there have been limited experimental precipitation observations to support this concept. We have combined satellite-based observations of the characteristics of EMIC waves, with satellite and ground-based observations of the EMIC-induced electron precipitation. In a detailed case study, supplemented by an additional four examples, we are able to constrain for the first time the location, size, and energy range of EMIC-induced electron precipitation inferred from coincident precipitation data and relate them to the EMIC wave frequency, wave power, and ion band of the wave as measured in situ by the Van Allen Probes. These observations will better constrain modeling into the importance of EMIC wave-particle interactions

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation