March 1971 wind tunnel tests of the Dorand DH 2011 jet flap rotor, volume 1

The results of wind tunnel tests, second series of tests performed in the NASA Ames 40 x 80 foot wind tunnel, of the DH 2011 jet-flap rotor are presented and analyzed. The tests have been focused on multicyclic effects and the capability of this rotor to reduce the vibratory loads and stresses in the blades. The reductions of the vibrations and stresses at tip speed ratio of 0.4 have attained 50%. The theory shows further reductions possible, reaching 80%. The results show that the performance characteristics after the modifications introduced since 1965 remained unchanged. The domain of investigation has been enlarged to include the tip speed ratios of 0.6 and 0.7. To analyze the complex aeroelastic phenomena a new analytical technique has been utilized to represent the mathematical model of the rotor. This technique, based on transfer matrices and transfer functions, appears very simple and it is believed that this analysis is applicable to many kinds of investigations involving large numbers of variables

March 1971 wind tunnel tests of the Dorand DH 2011 jet flap motor, volume 2

Wind tunnel tests were conducted of the Dorand DH 2011D jet flap rotor. The data recorded during the tests consist of: (1) multicyclic cam coefficients, (2) stress analysis, (3) vibratory loads, (4) Fourier analysis of flap deflection, and (5) blade bending stress. Data are presented in the form of tables and graphs

Diagnosis and workup of 522 consecutive patients with neuroendocrine neoplasms in Switzerland.

BACKGROUND: Neuroendocrine neoplasms (NENs) are difficult to diagnose. We used SwissNET data to characterise NEN patients followed in the two academic centres of western Switzerland (WS), and to compare them with patients followed in eastern Switzerland (ES) as well as with international guidelines. METHOD: SwissNET is a prospective database covering data from 522 consecutive patients (285 men, 237 women) from WS (n = 99) and ES (n = 423). RESULTS: Mean ± SD age at diagnosis was 59.0 ± 15.7 years. Overall, 76/522 experienced a functional syndrome, with a median interval of 1.0 (IQR: 1.0-3.0) year between symptoms onset and diagnosis. A total of 51/522 of these tumours were incidental. The primary tumour site was the small intestine (29%), pancreas (21%), appendix (18%) and lung (11%) in both regions combined. In all, 513 functional imaging studies were obtained (139 in WS, 374 in ES). Of these, 381 were 111In-pentetreotide scintigraphies and 20 were 68Ga-DOTATOC PET. First line therapy was surgery in 87% of patients, medical therapy (biotherapy or chemotherapy) in 9% and irradiation in 3% for both regions together. CONCLUSION: Swiss NEN patients appear similar to what has been described in the literature. Imaging by somatostatin receptor scintigraphy (SRS) is widely used in both regions of Switzerland. In good accordance with published guidelines, data on first line therapy demonstrate the crucial role of surgery. The low incidence of biotherapy suggests that long-acting somatostatin analogues are not yet widely used for their anti-proliferative effects. The SwissNET initiative should help improve compliance with ENETS guidelines in the workup and care of NEN patients

Allergen immunotherapy on the way to product-based evaluation - a WAO statement

Allergen immunotherapy (AIT) is widely used in clinical practice for patients with moderate to severe allergic rhinitis due to inhalant allergens and may be delivered via subcutaneous (SCIT) and sublingual routes (SLIT). However, the quality of evidence for individual AIT products is very heterogeneous, and extensions of overall conclusions ("class effects") on the efficacy and disease-modifying effects to all AIT products are unjustified. In contrast, each product needs to be evaluated individually, based on available study results, to justify efficacy and specific claims on sustained and disease modifying effects per allergen and targeted patient group (children vs. adults, allergic rhinitis vs. asthma). WAO intends to support the current development to evidence-based AIT, which ultimately will lead to a more efficacious treatment of allergic patients and the appropriate recognition of AIT

PeptX: Using Genetic Algorithms to optimize peptides for MHC binding

<p>Abstract</p> <p>Background</p> <p>The binding between the major histocompatibility complex and the presented peptide is an indispensable prerequisite for the adaptive immune response. There is a plethora of different <it>in silico </it>techniques for the prediction of the peptide binding affinity to major histocompatibility complexes. Most studies screen a set of peptides for promising candidates to predict possible T cell epitopes. In this study we ask the question vice versa: Which peptides do have highest binding affinities to a given major histocompatibility complex according to certain <it>in silico </it>scoring functions?</p> <p>Results</p> <p>Since a full screening of all possible peptides is not feasible in reasonable runtime, we introduce a heuristic approach. We developed a framework for Genetic Algorithms to optimize peptides for the binding to major histocompatibility complexes. In an extensive benchmark we tested various operator combinations. We found that (1) selection operators have a strong influence on the convergence of the population while recombination operators have minor influence and (2) that five different binding prediction methods lead to five different sets of "optimal" peptides for the same major histocompatibility complex. The consensus peptides were experimentally verified as high affinity binders.</p> <p>Conclusion</p> <p>We provide a generalized framework to calculate sets of high affinity binders based on different previously published scoring functions in reasonable runtime. Furthermore we give insight into the different behaviours of operators and scoring functions of the Genetic Algorithm.</p

In Vitro Evolution of Allergy Vaccine Candidates, with Maintained Structure, but Reduced B Cell and T Cell Activation Capacity

Allergy and asthma to cat (Felis domesticus) affects about 10% of the population in affluent countries. Immediate allergic symptoms are primarily mediated via IgE antibodies binding to B cell epitopes, whereas late phase inflammatory reactions are mediated via activated T cell recognition of allergen-specific T cell epitopes. Allergen-specific immunotherapy relieves symptoms and is the only treatment inducing a long-lasting protection by induction of protective immune responses. The aim of this study was to produce an allergy vaccine designed with the combined features of attenuated T cell activation, reduced anaphylactic properties, retained molecular integrity and induction of efficient IgE blocking IgG antibodies for safer and efficacious treatment of patients with allergy and asthma to cat. The template gene coding for rFel d 1 was used to introduce random mutations, which was subsequently expressed in large phage libraries. Despite accumulated mutations by up to 7 rounds of iterative error-prone PCR and biopanning, surface topology and structure was essentially maintained using IgE-antibodies from cat allergic patients for phage enrichment. Four candidates were isolated, displaying similar or lower IgE binding, reduced anaphylactic activity as measured by their capacity to induce basophil degranulation and, importantly, a significantly lower T cell reactivity in lymphoproliferative assays compared to the original rFel d 1. In addition, all mutants showed ability to induce blocking antibodies in immunized mice.The approach presented here provides a straightforward procedure to generate a novel type of allergy vaccines for safer and efficacious treatment of allergic patients

Glucocorticoid-related changes in body mass index among children and adolescents with rheumatic diseases

Objective To examine the temporal and dose-related effects of glucocorticoids (GCs) on body mass index (BMI) in children with rheumatic diseases. Methods Children initiating GCs for a rheumatic disease (n = 130) were assessed every 3 months for 18 months. BMI, weight, and height Z score trajectories were described according to GC starting dosage in prednisone equivalents: high (≥1.0 mg/kg/day), low (\u3c0.2 mg/kg/day to a maximum of 7.5 mg/day), and moderate (between high and low) dosage. The impact of GC dosing, underlying diagnosis, pubertal status, physical activity, and disease activity on BMI Z scores and on percent body fat was assessed with longitudinal mixed-effects growth curve models. Results The GC starting dose was high in 59% and moderate in 39% of patients. The peak BMI Z score was +1.29 at 4 months with high-dose GCs and +0.69 at 4.2 months with moderate-dose GCs (P \u3c 0.001). Overall, 50% (95% confidence interval 41-59%) of the children returned to within +0.25 SD of their baseline BMI Z score. Oral GC dose over the preceding 3 months was the most significant determinant of BMI Z score and percent body fat. The proportion of days in receipt of GCs, disease activity, and a diagnosis of systemic-onset juvenile idiopathic arthritis were also associated with BMI Z scores. The correlation between changes in BMI and changes in percent body fat was 0.09. Conclusion In children with rheumatic diseases starting moderate and high doses of GCs, BMI Z scores peaked at 4 months, and only half returned to within +0.25 SD of their baseline BMI Z score after 18 months. Copyright © 2013 by the American College of Rheumatology

Cytokine Profiles in Asthma Families Depend on Age and Phenotype

Background: Circulating cytokine patterns may be relevant for the diagnosis of asthma, for the discrimination of certain phenotypes, and prognostic factors for exacerbation of disease. Methodology/Principal Findings: In this study we investigated serum samples from 944 individuals of 218 asthma-affected families by a multiplex, microsphere based system detecting at high sensitivity eleven asthma associated mediators: eotaxin (CCL11), granulocyte macrophage stimulating factor (GM-CSF), interferon gamma (IFNγ), interleukin-4 (IL-4), IL-5, IL-8, IL-10, IL-12 (p40), IL-13, IL-17 and tumor necrosis factor alpha (TNFα). Single cytokine levels were largely similar between asthmatic and healthy individuals when analysing asthma as single disease entity. Regulatory differences between parental and pediatric asthma were reflected by six of the eleven mediators analyzed (eotaxin, IL-4, IL-5, IL-10, IL-12, TNFα). IL-12 (p40) and IL-5 were the best predictor for extrinsic asthma in children with an increased odds ratio of 2.85 and 1.96 per log pg/ml increase (IL-12 (p40): 1.2-6.8, p = 0.019, and IL-5: 1.2-2.5, p = 0.025). Frequent asthma attacks in children are associated with elevated IL-5 serum levels (p = 0.013). Cytokine patterns seem to be individually balanced in both, healthy and diseased adults and children, with various cytokines correlating among each other (IL-17 and IFNγ (rs = 0.67), IL-4 and IL-5 (rs = 0.55), IFNγ and GM-CSF (rs = 0.54)). Conclusion/Significance: Our data support mainly an age- but also an asthma phenotype-dependent systemic immune regulation. © 2010 Pukelsheim et al

Investigating the role of the interleukin-23/-17A axis in rheumatoid arthritis

Objective. IL-23 is a pro-inflammatory cytokine proposed to be central to the development of autoimmune disease. We investigated whether IL-23, together with the downstream mediator IL-17A, was present and functional in RA in humans

Phenotypic alterations in type II alveolar epithelial cells in CD4+ T cell mediated lung inflammation

<p>Abstract</p> <p>Background</p> <p>Although the contribution of alveolar type II epithelial cell (AEC II) activities in various aspects of respiratory immune regulation has become increasingly appreciated, our understanding of the contribution of AEC II transcriptosome in immunopathologic lung injury remains poorly understood. We have previously established a mouse model for chronic T cell-mediated pulmonary inflammation in which influenza hemagglutinin (HA) is expressed as a transgene in AEC II, in mice expressing a transgenic T cell receptor specific for a class II-restricted epitope of HA. Pulmonary inflammation in these mice occurs as a result of CD4⁺T cell recognition of alveolar antigen. This model was utilized to assess the profile of inflammatory mediators expressed by alveolar epithelial target cells triggered by antigen-specific recognition in CD4⁺T cell-mediated lung inflammation.</p> <p>Methods</p> <p>We established a method that allows the flow cytometric negative selection and isolation of primary AEC II of high viability and purity. Genome wide transcriptional profiling was performed on mRNA isolated from AEC II isolated from healthy mice and from mice with acute and chronic CD4⁺T cell-mediated pulmonary inflammation.</p> <p>Results</p> <p>T cell-mediated inflammation was associated with expression of a broad array of cytokine and chemokine genes by AEC II cell, indicating a potential contribution of epithelial-derived chemoattractants to the inflammatory cell parenchymal infiltration. Morphologically, there was an increase in the size of activated epithelial cells, and on the molecular level, comparative transcriptome analyses of AEC II from inflamed versus normal lungs provide a detailed characterization of the specific inflammatory genes expressed in AEC II induced in the context of CD4⁺T cell-mediated pneumonitis.</p> <p>Conclusion</p> <p>An important contribution of AEC II gene expression to the orchestration and regulation of interstitial pneumonitis is suggested by the panoply of inflammatory genes expressed by this cell population, and this may provide insight into the molecular pathogenesis of pulmonary inflammatory states. CD4⁺T cell recognition of antigen presented by AEC II cells appears to be a potent trigger for activation of the alveolar cell inflammatory transcriptosome.</p