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Ebola virus (EBOV) infection causes a high death toll, killing a high proportion of EBOV-infected patients within 7 days. Comprehensive data on EBOV infection are fragmented, hampering efforts in developing therapeutics and vaccines against EBOV. Under this circumstance, mathematical models become valuable resources to explore potential controlling strategies. In this paper, we employed experimental data of EBOV-infected nonhuman primates (NHPs) to construct a mathematical framework for determining windows of opportunity for treatment and vaccination. Considering a prophylactic vaccine based on recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (rVSV-EBOV), vaccination could be protective if a subject is vaccinated during a period from one week to four months before infection. For the case of a therapeutic vaccine based on monoclonal antibodies (mAbs), a single dose might resolve the invasive EBOV replication even if it was administrated as late as four days after infection. Our mathematical models can be used as building blocks for evaluating therapeutic and vaccine modalities as well as for evaluating public health intervention strategies in outbreaks. Future laborator experiments will help to validate and refine the estimates of the windows of opportunity proposed here.
Formation of Hubbard-like bands as a fingerprint of strong electron-electron interactions in FeSe
(2017)
We use angle-resolved photo-emission spectroscopy (ARPES) to explore the electronic structure of single crystals of FeSe over a wide range of binding energies and study the effects of strong electron-electron correlations. We provide evidence for the existence of "Hubbard-like bands" at high binding energies consisting of incoherent many-body excitations originating from Fe 3d states in addition to the renormalized quasiparticle bands near the Fermi level. Many high energy features of the observed ARPES data can be accounted for when incorporating effects of strong local Coulomb interactions in calculations of the spectral function via dynamical mean-field theory, including the formation of a Hubbard-like band. This shows that over the energy scale of several eV, local correlations arising from the on-site Coulomb repulsion and Hund's coupling are essential for a proper understanding of the electronic structure of FeSe and other related iron based superconductors.
We present the charged-particle multiplicity distributions over a wide pseudorapidity range (−3.4<η<5.0) for pp collisions at s√= 0.9, 7, and 8 TeV at the LHC. Results are based on information from the Silicon Pixel Detector and the Forward Multiplicity Detector of ALICE, extending the pseudorapidity coverage of the earlier publications and the high-multiplicity reach. The measurements are compared to results from the CMS experiment and to PYTHIA, PHOJET and EPOS LHC event generators, as well as IP-Glasma calculations.
The transverse momentum distributions of the strange and double-strange hyperon resonances (Σ(1385)±, Ξ(1530)0) produced in p-Pb collisions at sNN−−−√=5.02 TeV were measured in the rapidity range −0.5<yCMS<0 for event classes corresponding to different charged-particle multiplicity densities, ⟨dNch/dηlab⟩. The mean transverse momentum values are presented as a function of ⟨dNch/dηlab⟩, as well as a function of the particle masses and compared with previous results on hyperon production. The integrated yield ratios of excited to ground-state hyperons are constant as a function of ⟨dNch/dηlab⟩. The equivalent ratios to pions exhibit an increase with ⟨dNch/dηlab⟩, depending on their strangeness content.
The transverse momentum distributions of the strange and double-strange hyperon resonances (Σ(1385)±, Ξ(1530)0) produced in p-Pb collisions at sNN−−−√=5.02 TeV were measured in the rapidity range −0.5<yCMS<0 for event classes corresponding to different charged-particle multiplicity densities, ⟨dNch/dηlab⟩. The mean transverse momentum values are presented as a function of ⟨dNch/dηlab⟩, as well as a function of the particle masses and compared with previous results on hyperon production. The integrated yield ratios of excited to ground-state hyperons are constant as a function of ⟨dNch/dηlab⟩. The equivalent ratios to pions exhibit an increase with ⟨dNch/dηlab⟩, depending on their strangeness content.
We present the charged-particle multiplicity distributions over a wide pseudorapidity range (−3.4<η<5.0) for pp collisions at s√= 0.9, 7, and 8 TeV at the LHC. Results are based on information from the Silicon Pixel Detector and the Forward Multiplicity Detector of ALICE, extending the pseudorapidity coverage of the earlier publications and the high-multiplicity reach. The measurements are compared to results from the CMS experiment and to PYTHIA, PHOJET and EPOS LHC event generators, as well as IP-Glasma calculations.
Epigenetic control of microsomal prostaglandin E synthase-1 by HDAC-mediated recruitment of p300
(2017)
Nonsteroidal anti-inflammatory drugs are the most widely used medicine to treat pain and inflammation, and to inhibit platelet function. Understanding the expression regulation of enzymes of the prostanoid pathway is of great medical relevance. Histone acetylation crucially controls gene expression. We set out to identify the impact of histone deacetylases (HDACs) on the generation of prostanoids and examine the consequences on vascular function. HDAC inhibition (HDACi) with the pan-HDAC inhibitor, vorinostat, attenuated prostaglandin (PG)E2 generation in the murine vasculature and in human vascular smooth muscle cells. In line with this, the expression of the key enzyme for PGE2 synthesis, microsomal PGE synthase-1 (PTGES1), was reduced by HDACi. Accordingly, the relaxation to arachidonic acid was decreased after ex vivo incubation of murine vessels with HDACi. To identify the underlying mechanism, chromatin immunoprecipitation (ChIP) and ChIP-sequencing analysis were performed. These results suggest that HDACs are involved in the recruitment of the transcriptional activator p300 to the PTGES1 gene and that HDACi prevented this effect. In line with the acetyltransferase activity of p300, H3K27 acetylation was reduced after HDACi and resulted in the formation of heterochromatin in the PTGES1 gene. In conclusion, HDAC activity maintains PTGES1 expression by recruiting p300 to its gene.
The yeast Rcf1 protein is a member of the conserved family of proteins termed the hypoxia-induced gene (domain) 1 (Hig1 or HIGD1) family. Rcf1 interacts with components of the mitochondrial oxidative phosphorylation system, in particular the cytochrome bc1 (complex III)-cytochrome c oxidase (complex IV) supercomplex (termed III-IV) and the ADP/ATP carrier proteins. Rcf1 plays a role in the assembly and modulation of the activity of complex IV; however, the molecular basis for how Rcf1 influences the activity of complex IV is currently unknown. Hig1 type 2 isoforms, which include the Rcf1 protein, are characterized in part by the presence of a conserved motif, (Q/I)X3(R/H)XRX3Q, termed here the QRRQ motif. We show that mutation of conserved residues within the Rcf1 QRRQ motif alters the interactions between Rcf1 and partner proteins and results in the destabilization of complex IV and alteration of its enzymatic properties. Our findings indicate that Rcf1 does not serve as a stoichiometric component, i.e. as a subunit of complex IV, to support its activity. Rather, we propose that Rcf1 serves to dynamically interact with complex IV during its assembly process and, in doing so, regulates a late maturation step of complex IV. We speculate that the Rcf1/Hig1 proteins play a role in the incorporation and/or remodeling of lipids, in particular cardiolipin, into complex IV and. possibly, other mitochondrial proteins such as ADP/ATP carrier proteins.
In this proceeding, we study the dynamical evolution of the sigma field within the framework of Langevin dynamics. We find that, as the system evolves in the critical regime, the magnitudes and signs of the cumulants of sigma field, C3 and C4, can be dramatically different from the equilibrated ones due to the memory effects near Tc. For the dynamical evolution across the 1st order phase transition boundary, the supercooling effect leads the sigma field to be widely distributed in the thermodynamical potential, which largely enhances the cumulants C3, C4, correspondingly.