Moduli backreaction and supersymmetry breaking in string-inspired inflation models

We emphasize the importance of effects from heavy fields on supergravity models of inflation. We study, in particular, the backreaction of stabilizer fields and geometric moduli in the presence of supersymmetry breaking. Many effects do not decouple even if those fields are much heavier than the inflaton field. We apply our results to successful models of Starobinsky-like inflation and natural inflation. In most scenarios producing a plateau potential it proves difficult to retain the flatness of the potential after backreactions are taken into account. Some of them are incompatible with non-perturbative moduli stabilization. In natural inflation there exist a number of models which are not constrained by backreactions at all. In those cases the correction terms from heavy fields have the same inflaton-dependence as the uncorrected potential, so that inflation may be possible even for very large gravitino masses.Comment: 29 pages, 1 figure, comments added, subsection 2.3 added, published versio

Quantitative X-ray Tomography of the Mouse Cochlea

Imaging with hard X-rays allows visualizing cochlear structures while maintaining intrinsic qualities of the tissue, including structure and size. With coherent X-rays, soft tissues, including membranes, can be imaged as well as cells making use of the so-called in-line phase contrast. In the present experiments, partially coherent synchrotron radiation has been used for micro-tomography. Three-dimensional reconstructions of the mouse cochlea have been created using the EM3D software and the volume has been segmented in the Amira Software Suite. The structures that have been reconstructed include scala tympani, scala media, scala vestibuli, Reissner's membrane, basilar membrane, tectorial membrane, organ of Corti, spiral limbus, spiral ganglion and cochlear nerve. Cross-sectional areas of the scalae were measured. The results provide a realistic and quantitative reconstruction of the cochlea

Genomic Expression Libraries for the Identification of Cross-Reactive Orthopoxvirus Antigens

Increasing numbers of human cowpox virus infections that are being observed and that particularly affect young non-vaccinated persons have renewed interest in this zoonotic disease. Usually causing a self-limiting local infection, human cowpox can in fact be fatal for immunocompromised individuals. Conventional smallpox vaccination presumably protects an individual from infections with other Orthopoxviruses, including cowpox virus. However, available live vaccines are causing severe adverse reactions especially in individuals with impaired immunity. Because of a decrease in protective immunity against Orthopoxviruses and a coincident increase in the proportion of immunodeficient individuals in today's population, safer vaccines need to be developed. Recombinant subunit vaccines containing cross-reactive antigens are promising candidates, which avoid the application of infectious virus. However, subunit vaccines should contain carefully selected antigens to confer a solid cross-protection against different Orthopoxvirus species. Little is known about the cross-reactivity of antibodies elicited to cowpox virus proteins. Here, we first identified 21 immunogenic proteins of cowpox and vaccinia virus by serological screenings of genomic Orthopoxvirus expression libraries. Screenings were performed using sera from vaccinated humans and animals as well as clinical sera from patients and animals with a naturally acquired cowpox virus infection. We further analyzed the cross-reactivity of the identified immunogenic proteins. Out of 21 identified proteins 16 were found to be cross-reactive between cowpox and vaccinia virus. The presented findings provide important indications for the design of new-generation recombinant subunit vaccines

Profit enhancing competitive pressure in vertically related industries

Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Detection of poxvirus in cattle associated with human cases in the State of Rio de Janeiro: preliminary report

This preliminary report describes human and cow cases of poxvirus that recently ocurred in the State of Rio de Janeiro. The electron microscopic findings were consistent with parapoxviral and orthopoxviral infection. Orthopoxvirus strains were isolated from human and cow cases. Detailed viral characterization by means of genetical techniques is under investigation. Based on these informations, poxviral diseases should be also considered an emerging viral zoonosis that can affect human beings