The production and development of H7 Influenza virus pseudotypes for the study of humoral responses against avian viruses

In recent years, high pathogenicity avian influenza (HPAI) virus, H5N1, low pathogenicity avian influenza (LPAI) virus, H9N2, and both HPAI and LPAI H7 viruses have proved devastating for the affected economies reliant on poultry industry, and have posed serious public health concerns. These viruses have repeatedly caused zoonotic disease in humans, raising concerns of a potential influenza pandemic. Despite the focus on the HPAI H5N1 outbreak in 1997 some H7 strains have also shown to be occasionally adaptable to infecting humans. Therefore, applying knowledge of the H5 virus evolution and spread to the development of sensitive serological methods is likely to improve our ability to understand and respond to the emergence of other HPAI and LPAI viruses, present within the avian populations, with the potential to infect humans and other species. In the present study we describe the construction and production of lentiviral pseudotypes bearing envelope glycoproteins of LPAI and HPAI H7 avian influenza viruses, which have been responsible for several outbreaks in the past decade. The H7 pseudotypes were evaluated in pseudotype-based neutralization (pp-NT) assays in order to detect and quantify the presence of neutralizing antibodies in avian sera, which were confirmed H7 positive by inhibition of haemagglutination (HI) test. Overall, our results substantiate influenza virus pseudotype neutralization as a robust tool for influenza sero-surveillance

The use of equine influenza pseudotypes for serological screening

Standard assays used for influenza serology present certain practical issues, such as inter-laboratory variability, complex protocols and the necessity for handling certain virus strains in high biological containment facilities. In an attempt to address this, avian and human influenza HA pseudotyped retroviruses have been successfully employed in antibody neutralization assays. In this study we generated an equine influenza pseudotyped lentivirus for serological screening. This was achieved by co-transfection of HEK293T cells with plasmids expressing the haemagglutinin (HA) protein of an H3N8 subtype equine influenza virus strain, HIV gag-pol and firefly luciferase reporter genes and harvesting virus from supernatant. In order to produce infective pseudotype particles it was necessary to additionally co-transfect a plasmid encoding the TMPRSS2 endoprotease to cleave the HA. High titre pseudotype virus (PV) was then used in PV antibody neutralization assays (PVNAs) to successfully distinguish between vaccinated and non-vaccinated equines. The sera were also screened by single radial haemolysis (SRH) assay. There was a 65% correlation between the results of the two assays, with the PVNA assay appearing slightly more sensitive. Future work will extend the testing of the PVNA with a larger number of serum samples to assess sensitivity/specificity, inter/intra-laboratory variability and to define a protective titre

Propranolol as first-line treatment for life-threatening diffuse infantile hepatic hemangioma: a case report

[No abstract available

Teaching as a decision-making model: strategies in mathematics from a practical requirement

The need in the current social context to adopt teaching methods that can stimulate students and lead them towards autonomy, awareness and independence in studying could conflict with the needs of students with specific learning disorders, especially in higher education, where self-learning and self-orientation are required. In this sense, the choice of effective teaching strategies becomes a decision-making problem and must therefore be addressed as such. This article discusses some mathematical models for choosing effective methods in mathematics education for students with specific learning disorders. It moves from the case study of a student with specific reading and writing disorders enrolled in the mathematical analysis course 1 of the degree course in architecture and describes the personalized teaching strategy created for him

Duality, Compactification, and e−1/λe^{-1/\lambda} Effects in the Heterotic String Theory

Two classes of stringy instanton effects, stronger than standard field theory instantons, are identified in the heterotic string theory. These contributions are established using type IIA/heterotic and type I/heterotic dualities. They provide examples for the heterotic case of the effects predicted by Shenker based on the large-order behavior of perturbation theory. The corrections vanish as the radius of the compactification goes to infinity. For appropriate amplitudes, they are computable worldsheet or worldline instanton effects on the dual side. Some potential applications are discussed.Comment: 11 pages, harvmac bi

On the Grassmann space representing the lines of an affine space

AbstractIn 1982, Bichara and Mazzocca characterized the Grassmann space Gr(1,A) of the lines of an affine space A of dimension at least 3 over a skew-field K by means of the intersection properties of the three disjoint families Σ1,Σ2 and T of maximal singular subspaces of Gr(1,A). In this paper, we deal with the characterization of Gr(1,A) using only the family Σ=Σ1∪Σ2 of maximal singular subspaces

SUSY Gauge Dynamics and Singularities of 4d N=1 String Vacua

Many N=1 heterotic string compactifications exhibit physically mysterious singularities at codimension one in the moduli space of vacua. At these singularities, Yukawa couplings of charged fields develop poles as a function of the moduli. We explain these conformal field theory singularities, in a class of examples, as arising from non-perturbative gauge dynamics of non-perturbative gauge bosons (whose gauge coupling is the sigma model coupling) in the string theory.Comment: 17 pages, harvmac bi

Quality of Higher Education through the Pursuit of Satisfaction with a Focus on Sustainability

The objective of this study is to analyse individual differences in quality of higher education through the pursuit of satisfaction with a focus on sustainability, whilst considering variables pertaining to groups (family, teachers and pupils) and satisfaction in a sample of 1091 Italians: 510 pupils (45.8%), 121 teachers (11.1%) and 469 relatives (42.9%). Once the quality parameters of the instrument (quality of higher education through the pursuit of satisfaction with a focus on the sustainability (QHES) questionnaire) were determined, reliability was confirmed through confirmatory factor analysis using structural equation modelling methodology, and data collection was initiated. Results from the multi-level study (ANOVA) showed significant differences between groups. From this, it can be concluded from the study that the role performed by a quality education oriented towards sustainability equally includes teachers, students and relatives. This role focuses on the battle to incorporate effective participatory methods into the teaching process, motivating members of the educational community and social future in the search for knowledge, skills, attitudes and necessary values. This will forge a sustainable future given that it does not only depend on the characteristics and experiences of individuals but also their training, both within the centre and their families. This factor is of vital importance, as demonstrated and concluded in the present study.This research received external funding by Project HUM-983 (ITACA): “Research through transforming learning and contexts.”

Evaluating Deep Learning-based Melanoma Classification using Immunohistochemistry and Routine Histology: A Three Center Study

Pathologists routinely use immunohistochemical (IHC)-stained tissue slides against MelanA in addition to hematoxylin and eosin (H&E)-stained slides to improve their accuracy in diagnosing melanomas. The use of diagnostic Deep Learning (DL)-based support systems for automated examination of tissue morphology and cellular composition has been well studied in standard H&E-stained tissue slides. In contrast, there are few studies that analyze IHC slides using DL. Therefore, we investigated the separate and joint performance of ResNets trained on MelanA and corresponding H&E-stained slides. The MelanA classifier achieved an area under receiver operating characteristics curve (AUROC) of 0.82 and 0.74 on out of distribution (OOD)-datasets, similar to the H&E-based benchmark classification of 0.81 and 0.75, respectively. A combined classifier using MelanA and H&E achieved AUROCs of 0.85 and 0.81 on the OOD datasets. DL MelanA-based assistance systems show the same performance as the benchmark H&E classification and may be improved by multi stain classification to assist pathologists in their clinical routine

Elexacaftor-Tezacaftor-Ivacaftor corrects monocyte microbicidal deficiency in cystic fibrosis

Question. Cystic Fibrosis (CF), which is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), is characterized by chronic bacterial lung infection and inflammation. In CF, monocytes and monocyte-derived macrophages have been shown to display defective phagocytosis and antimicrobial activity against relevant lung pathogens, including Pseudomonas aeruginosa. Thus, we addressed the effect of the CFTR triple modulator therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI), on the activity of CF monocytes against P. aeruginosa. Materials/patients and Methods Monocytes from people with CF (PWCF) before and after 1 and 6 months of ETI therapy were isolated from blood and infected with P. aeruginosa to assess phagocytic activity and intracellular bacterial killing. The oxidative burst and IL-6 secretion were also determined. Monocytes from healthy controls were also included. Results and answer to the question Longitudinal analysis of the clinical parameters confirmed an improvement of lung function and lung microbiology by ETI. Both the phagocytic and microbicidal deficiencies of the CF monocytes also improved significantly, although not completely. Furthermore, we measured an exuberant oxidative burst in CF monocytes before therapy, which was reduced considerably by ETI. This led to an improvement of the ROS-dependent bactericidal activity. Inflammatory response to bacterial stimuli was also lowered compared to pre-therapy. PWCF on ETI therapy, in a real-life setting, in addition to clinical recovery, showed significant improvement in monocyte activity against P. aeruginosa, which may have contributed to the overall effect of ETI on pulmonary disease. This also suggests that CF monocyte dysfunctions may be specifically targeted to ameliorate lung function in CF