Immunization with a dominant-negative recombinant Herpes Simplex Virus (HSV) type 1 protects against HSV-2 genital disease in guinea pigs

<p>Abstract</p> <p>Background</p> <p>CJ9-gD is a novel dominant-negative recombinant herpes simplex virus type 1 (HSV-1) that is completely replication-defective, cannot establish detectable latent infection <it>in </it>vivo, and expresses high levels of the major HSV-1 antigen glycoprotein D immediately following infection. In the present study, CJ9-gD was evaluated as a vaccine against HSV-2 genital infection in guinea pigs.</p> <p>Results</p> <p>Animals immunized with CJ9-gD developed at least 700-fold higher titers of HSV-2-specific neutralization antibodies than mock-immunized controls. After challenge with wild-type HSV-2, all 10 control guinea pigs developed multiple genital lesions with an average of 21 lesions per animal. In contrast, only 2 minor lesions were found in 2 of 8 CJ9-gD-immunized animals, representing a 40-fold reduction on the incidence of primary genital lesions in immunized animals (p < 0.0001). Immunization significantly reduced the amount and duration of viral shedding and provided complete protection against neurological symptoms, while 90% of mock-immunized animals succumbed due to the severity of disease. Importantly, immunized animals showed no signs of recurrent disease or viral shedding during a 60-days observation period after recovery from primary infection, and carried 50-fold less latent viral DNA load in their dorsal root ganglia than the surviving mock-vaccinated controls (p < 0.0001).</p> <p>Conclusions</p> <p>Collectively, we demonstrate that vaccination with the HSV-1 recombinant CJ9-gD elicits strong and protective immune responses against primary and recurrent HSV-2 genital disease and significantly reduces the extent of latent infection.</p

Specialized enterprise service bus of an enterprise

At the modern companies the large number of information systems (IS) of various levels and purposes is used, and also new IS are periodically being implemented. The problem of the IS integration (their functions and data) becomes vital at a certain stage of the development of any company. The concept of service-oriented architecture (SOA) is considered as one of the most perspective concepts during the solution of problems of the IS integration for the creation of new IS of corporate level and their integration with the systems existing at the companies. The central connective software component of the SOA concept is the enterprise service bus (ESB). In the article the analysis of the most popular existing ESB and integration platforms for development of new ESB is carried out. It is shown that the most part of the existing ESB is functionally excessive, has high price and demands the essential additional development with specifics of a company during the ESB creation on a platform basis. That is why the way of the creation of new specialized ESB is perspective. In the article it is shown that a framework which is sufficient for the development of specialized inexpensive ESB is the .NET framework. Functionality of the created specialized ESB and features of its program implementation are considered. Results of the efficiency researches of the specialized ESB and its comparative analysis with ESB of the most popular producers are given

Which outcomes have been measured in hand eczema trials? A systematic review:A systematic review

The considerable heterogeneity of outcomes and measurement instruments in hand eczema trials substantially limits the evidence synthesis concerning therapeutic and preventive interventions. Therefore, the Hand Eczema Core Outcome Set (HECOS) initiative is developing a core outcome set for future trials. The first objective was to identify outcomes that were measured in previous trials, to group them in domains, and to identify their measurement instruments. We conducted a systematic review of controlled and randomized controlled hand eczema trials published since 2000. Sixty-one eligible studies were identified. Each assessed one or more of 47 outcomes in the "skin" domain. Eighteen trials (30%) additionally focused on preventive behaviour in risk occupations. Quality of life was measured in 13 studies (21%). Thirty-two distinct named instruments were applied, but 223 measurements (62%) were conducted with unnamed instruments. Only 32 studies (52%) defined a primary outcome. Twenty-nine trials (48%) provided some information on adverse events, but none gave any references concerning relevant methods. Our review confirms the need to harmonize outcome measurements in hand eczema trials. The findings form the basis for a consensus process to generate a core outcome set to improve the explanatory power and comparability of future hand eczema studies.</p

Integrin αE(CD103) Is Involved in Regulatory T-Cell Function in Allergic Contact Hypersensitivity

Murine contact hypersensitivity (CHS) is a dendritic cell (DC)-dependent T-cell-mediated inflammation with CD8+ T cells as effectors and CD4+ T cells as regulators (Treg cells) that models human allergic contact dermatitis. The integrin αE(CD103) is expressed by some T-cell and DC subsets and has been implicated in epithelial lymphocyte localization, but its role in immune regulation remains enigmatic. We have identified a function for CD103 in the development of cutaneous allergic immune responses. CHS responses, but not irritant contact dermatitis, were significantly augmented in CD103-deficient mice in hapten-challenged skin. Phenotype and function of skin DCs during sensitization were normal, whereas adoptive transfer experiments revealed that the elevated CHS response in CD103-deficient mice is transferred by primed T cells and is independent of resident cells in recipient mice. While T-cell counts were elevated in challenged skin of CD103-deficient mice, the FoxP3 expression level of CD4+CD25+ Treg cells was significantly reduced, indicating impaired functionality. Indeed, Treg cells from CD103-deficient mice were not able to suppress CHS reactions during the elicitation phase. Further, CD103 on FoxP3+ Treg cells was involved in Treg retention to inflamed skin. These findings indicate an unexpected dichotomous functional role for CD103 on Treg cells by modulating FoxP3 expression

Vacuum fluctuations in axion-dilaton cosmologies

We study axion-dilaton cosmologies derived from the low-energy string effective action. We present the classical homogeneous Friedmann-Robertson-Walker solutions and derive the semi-classical perturbation spectra in the dilaton, axion and moduli fields in the pre-Big Bang scenario. By constructing the unique S-duality invariant field perturbations for the axion and dilaton fields we derive S-duality invariant solutions, valid when the axion field is time-dependent as well as in a dilaton-vacuum cosmology. Whereas the dilaton and moduli fields have steep blue perturbation spectra (with spectral index n=4) we find that the axion spectrum depends upon the expansion rate of the internal dimensions (0.54<n<4) which allows scale-invariant (n=1) spectra. We note that for n<1 the metric is non-singular in the conformal frame in which the axion is minimally coupled.Comment: LaTeX, 23 pages plus 6 figures, minor typos corrected and references updated. To appear in Phys Rev

Patch test results with the European baseline series, 2019/20-Joint European results of the ESSCA and the EBS working groups of the ESCD, and the GEIDAC

BACKGROUND Continual analyses of patch test results with the European baseline series (EBS) serve both contact allergy surveillance and auditing the value of included allergens. OBJECTIVES To present results of current EBS patch testing, obtained in 53 departments in 13 European countries during 2019 and 2020. METHODS Anonymised or pseudonymised individual data, and partly aggregated data on demographic/clinical characteristics and patch test rest results with the EBS were prospectively collected and centrally pooled and analysed. RESULTS In 2019 and 2020, 22581 patients were patch tested with the EBS. Sensitization to nickel remained most common (19.8 (19.2-20.4)% positivity (95% confidence interval)). Fragrance mix I and Myroxylon pereirae yielded very similar results with 6.80 (6.43-7.19)% and 6.62 (6.25-7.00)% positivity, respectively. Formaldehyde at 2% aq. yielded almost one percentage point more positive reactions than 1% concentration (2.49 (2.16-2.85)% vs. 1.59 (1.33-1.88)); methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI alone up to around 5% positives. Among the new additions, propolis was most commonly positive (3.48 (3.16-3.82)%), followed by 2-hydroxyethyl methacrylate (2.32 (2.0-2.68)%). CONCLUSIONS Ongoing surveillance on the prevalence of contact sensitization contributes to an up-to-date baseline series containing the most frequent and/or relevant contact sensitizers for routine patch testing in Europe. This article is protected by copyright. All rights reserved

An online platform supporting the analysis of water adaptation measures in the Alps

Climate change may result in reduced water supply from the Alps - an important water resource for Europe. This paper presents a multilingual platform that combines spatial and multi-criteria decision-support tools to facilitate stakeholder collaboration in the analysis of water management adaptation options. The platform has an interactive map interface that allows participants to select a location of their interest within the Alpine Arc. By utilising the decision-support tool, stakeholders can identify suitable adaptation solutions for different geographical units, according to their experience and preference. The platform was used to involve experts across Alpine borders, domains and decision-making levels, as well as a group of university students. The experts favoured the planning instruments for saving water, while the students inclined towards the measures that would improve water conservation. The initial results confirmed the suitability of the platform for future involvement of decision-makers in spatio-temporal analyses of adaptation pathways in the Alps

Acoustic attenuation spectroscopy and helium ion microscopy study of rehydration of dairy powder

Complete hydration is essential for the production of structured dairy products from powders. It is essential that the ingredients used hydrate completely. Determination of an end point of rehydration is non-trivial, but ultrasound-based methodologies have demonstrated potential in this area and are well suited to measuring bulk samples in situ. Here, acoustic attenuation spectroscopy (AAS) is used to monitor rehydration of skim milk powder, and recombined systems of micellar casein isolate with lactose and whey protein isolate. Dynamic light scattering, zeta-potential measurements and AAS as a function of pH characterise each component around its isoelectric point to assess its functionality. Scanning helium ion microscopy was used to image the dry powders, without any conductive coating, producing resolution equivalent to scanning electron microscopy, but with much larger focal lengths and fewer imaging artefacts. Imaging the powders provides information on particle size and morphology which can affect dissolution behaviour. Reconstituted skim milk powder and recombined samples were monitored showing there are changes occurring over several hours. Attenuation coefficients are shown to predict the end point of hydration. Model fitting is used to extract volume fractions and average particle sizes of large and small particle populations in recombined samples over time. AAS is demonstrated to be capable of tracking the dynamics in rehydrating dispersions over time. Physical parameters such as the volume fraction and particle size of the dispersed phase can be determined

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema