Roche (Austria)

Abstract In the framework of the Horizon Europe project SETO we investigated the integration of the RAMSHEEP and reliability analysis into bridge asset management and life cycle cost analysis with special emphasis on the impact of overloading of vehicles on bridge service life and availability in the context of an ageing bridge stock. For this we conducted an extensive investigation into bridge costs for construction, rehabilitation and operation, different performance functions and impact of rehabilitation measures. Based on the age distribution and standardized bridge life cycles we investigated current challenges regarding investment needs and possible strategies to ensure a reliable, available and safe bridge network based on the bridge network of regional roads in the province of Styria, Austria.

Abstract With increasing risks from natural hazards in alpine regions in Austria OEBB‐Infra and Hoffmann‐Consult have developed a consistent methodology for condition assessment, prediction, and life cycle optimization of protective structures. Based on a thorough assessment of the asset stock standardized life cycles for key structures like rockfall and avalanche protection structures have been derived. The developed life cycle models allow a generalized assessment of asset condition, residual service life, and remaining asset value. In contrast to typical transport assets, protective structures are both subject to natural aging processes and random events with a certain occurrence rate. Beyond standardized life cycles on network level an adjustment to project level is necessary to account for actual condition development and asset specific events. The paper provides an overview on the developed generic life cycle with application to rockfall protection structures with prices 2022 in Austria.

Systematic analyses of market developments and transport trends are the basis for the evaluation of investments in transport infrastructure in common approval procedures. Traditional cost benefit analysis (CBA) considers time savings between connected locations as a key benefit of the expansion of transport infrastructure. With reference to almost constant time expenditures for mobility, some researchers argue that there are no relevant time savings and thus no real benefits. As the literature analysis and empirical data show, both the time savings between locations after expansion and approximately constant time expenditures for mobility in the transport system over the long term can be observed. Resolving this issue is therefore the key for consistent economic analysis of transport infrastructure investments. Using a location-theoretic model and empirical data, the paper shows that expansion projects reduce transportation costs, increase efficiency, and largely translate the time savings into accessibility benefits. The centralized production and division of labor is then the basis for economies of scale efficiency gains with diminishing marginal utility. As the resulting environmental impacts and resource consumption are not adequately reflected in standard economic theory, the development in transport is largely unsustainable yielding high external costs. A possible solution would thus be to contrast the efficiency gains in the market with the life cycle costs and external costs of these investments.

The history of placebo goes back several centuries. These “dummy pills” have been used by healers and physicians worldwide, ignored by the official medical community [1]. In 1931, Amberson et al. introduced the concept of experimental randomization to medical research via a study on tuberculosis treatment. They randomized 24 tuberculosis patients into two groups, one group receiving sanocrysin for treatment, the other group distilled water. The randomization was performed by flipping a coin [2]. Substances or medical procedures should be considered within a complex psychosocial context that may influence the therapeutic outcome [3]. A placebo can be any clinical intervention including gestures, words, devices, pills, and surgery. In context with surgery, the term sham is sometimes used to describe such a placebo intervention [4]. To dissect this psychosocial effect and to reject the specific action of the therapy, a dummy treatment, the placebo, is given which makes the patient believe to be effectively treated. The response to this treatment, the placebo effect, is also known under such terms as expectancy effect, context effect, and meaning response. The real placebo effect is a psychobiological phenomenon that can be the result of different mechanisms including the anticipation of clinical benefit and Pavlovian conditioning [3]. Various studies suggest that there are physical aspects influencing people’s perceptions, e.g., the color and size of the pills. Others report that capsules are experienced to have stronger effects than tablets. Injections trigger a stronger placebo response than oral medication and surgery elicits probably the highest rates in placebo response [4]. It has been reported that placebos may improve subjective and objective outcomes in up to 30–40 % of patients with a wide range of clinical conditions, considering that the placebo effect cannot be distinguished from the natural course of the disease, regression to the mean, and the effects of other factors. In general, the presence of pain and anxiety, the involvement of immunobiochemical processes, and the autonomic nervous system are supposed to respond expediently to placebo, whereas chronic degenerative diseases, hyperacute illnesses like heart attacks and hereditary diseases are anticipated to resist [1].

Influenza virus uses a unique cap-snatching mechanism characterized by hijacking and cleavage of host capped pre-mRNAs, resulting in short capped RNAs, which are used as primers for viral mRNA synthesis. The PA subunit of influenza polymerase carries the endonuclease activity that catalyzes the host mRNA cleavage reaction. Here, we show that PA is a sequence selective endonuclease with distinct preference to cleave at the 3′ end of a guanine (G) base in RNA. The G specificity is exhibited by the native influenza polymerase complex associated with viral ribonucleoprotein particles and is conferred by an intrinsic G specificity of the isolated PA endonuclease domain PA-Nter. In addition, RNA cleavage site choice by the full polymerase is also guided by cap binding to the PB2 subunit, from which RNA cleavage preferentially occurs at the 12th nt downstream of the cap. However, if a G residue is present in the region of 10–13 nucleotides from the cap, cleavage preferentially occurs at G. This is the first biochemical evidence of influenza polymerase PA showing intrinsic sequence selective endonuclease activity.

Patients with multiple sensitizations require alternative forms of treatment, as the efficacy of conventional immunotherapy is unsatisfactory. In the present study, we sought to compare the efficacy of a subcutaneously (s.c.) and a mucosally applied polyvalent vaccine to reduce allergic immune responses within airway and lung tissues. Female BALB/c mice were intraperitoneally immunized with recombinant (r)Bet v 1, rPhl p 1 and rPhl p 5, followed by an aerosol challenge of birch and phleum pollen extract. For tolerance induction, either a mixture of the immunodominant peptides or a hybrid peptide of the respective antigens was s.c. injected or intranasally applied before poly-sensitization. Mucosal but not systemic pre-treatment with poly-peptides led to significant suppression of eosinophils and IL-5 production in bronchoalveolar lavages, as well as IL-5, IL-4, IL-13 and eotaxin levels in lung cell cultures. Lung histology showed a clear reduction of cellular infiltration and mucus production only in intranasally pre-treated mice. In accordance, also the systemic immune response, characterized by IgE-dependent basophil degranulation and IL-4 levels in vitro, was significantly reduced by mucosal antigen application, but only marginally influenced by subcutaneous pre-treatment. Both treatment routes led to up-regulated CTLA4 expression in splenocytes, whereas only after mucosal pre-treatment Foxp3 expression levels were enhanced in lung CD3(+) T cells. Furthermore, intranasal but not subcutaneous application of the peptides enhanced IL-10 levels in the lungs, indicating regulatory mechanisms operating in local tolerance induction. Mucosal application of peptides is superior to systemic application in preventing both local and systemic poly-allergic T helper2 immune responses, suggesting mucosal tolerance induction as an attractive strategy for the primary and secondary prevention of allergic multi-sensitization and lung pathology.

Many aspects of optical chemical sensor design would benefit from a better knowledge of the diffusion properties of the analyte in the polymer host. The response times of such sensors to a step change of analyte concentration are of vital interest for many applications of fast-responding sensors. Further, the diffusion properties govern their quenching behavior and their sensitivity. A method for determination of the diffusion constant of oxygen in polymers has been developed and used by several groups in the past. The underlying mathematical model for luminescence quenching by molecules of a gas in a single sensing layer on an impermeable support has not yet been completely derived in an analytical form and still uses tedious numerical methods. We present a partial analytical solution to the problem of modeling the time dependence of luminescence generated by in- or out-diffusion of a gaseous quencher in a polymer film in which a luminophor is immobilized and offer a suitable method to predict sensor response times.

In this study, we established a fully automated molecular assay for qualitative detection of hepatitis C virus (HCV) in serum and whole-blood samples and compared it with conventional molecular assays, including manual HCV RNA extraction protocols. Whole-blood samples were collected from patients with and without chronic HCV infection in EDTA tubes and nucleic acid stabilization tubes (NASTs). Prior to HCV RNA extraction, the HCV Internal Control (IC), derived from the COBAS AMPLICOR HCV test, version 2.0 (Roche Molecular Diagnostics), was added. The new assay was based on an automated extraction protocol on the MagNA Pure LC instrument (Roche Applied Science), followed by automated reverse transcription, amplification, hybridization, and detection on the Cobas Amplicor analyzer (Roche Molecular Diagnostics). The detection limit of the new assay was found to be similar to those of conventional molecular assays. In clinical samples, 100% agreement between the new assay and conventional methods was observed. The introduced amount of IC was detected in 45 of 45 serum samples, 41 of 45 EDTA tube whole-blood samples, and 43 of 45 NAST whole-blood samples. Retesting led to more frequent IC detection. The fully automated molecular assay was found to be suitable for detection of HCV RNA in different kinds of sample materials. It may be recommended for use in the high-throughput routine molecular diagnostic laboratory.