Mechanics of the Ski-Snow Contact

Two outstanding questions of the ski-snow friction are considered: the deformation mode of the snow and the real contact area. The deformation of hard, well sintered snow in a short time impact has been measured with a special linear friction tester. Four types of deformations have been identified: brittle fracture of bonds, plastic deformation of ice at the contact spots, elastic and delayed elastic deformation of the snow matrix. The latter is the dominant deformation in the ski-snow contact. Based on the measured loading curves the mechanical energy dissipation of snow deformation in skiing on hard snow has been determined and found negligible compared to the thermal energy dissipation. A mechanical model consisting of ice spheres supported by rheological elements (a non-linear spring in series with a Kelvin element) is proposed to model the deformation of snow in the ski-snow contact. The model can describe the delayed elastic behaviour of snow. Coupled with the complete topographical description of the snow surface obtained from X-ray micro computer tomography measurements, the model predicts the number and area of contact spots between ski and snow. An average contact spot size of 110μm, and a relative real contact area of 0.4% has been foun

Sliding friction of polyethylene on ice: tribometer measurements

: It is well known that the low kinetic friction experienced when sliding on snow and ice is due to water films generated through frictional heating. There is, however, uncertainty concerning the thickness and the distribution of these water films. Since direct observation of the water films is difficult, tribometer studies coupled with temperature measurements have been carried out on a large-scale, pin-on-disc tribometer (diameter 1.80m). IR sensors were used to measure the temperature of the ice track in front of and behind the contact region. In addition, thermocouples integrated into the polyethylene slider measured the temperature close to the interface. The kinetic friction between polyethylene and ice has been measured as a function of temperature, velocity, load, and apparent contact area. The friction coefficient, as well as the temperature increase of the slider and the ice track, depends on all of these parameters. Interpretation of the results is given on the basis of hydrodynamic lubrication, taking into account the generation and shearing of thin water films in the contact region

IFKIS - a basis for managing avalanche risk in settlements and on roads in Switzerland

After the avalanche winter of 1999 in Switzerland, which caused 17&nbsp;deaths and damage of over CHF&nbsp;600&nbsp;mill. in buildings and on roads, the project IFKIS, aimed at improving the basics of organizational measures (closure of roads, evacuation etc.) in avalanche risk management, was initiated. <P style='line-height: 20px;'> The three main parts of the project were the development of a compulsory checklist for avalanche safety services, a modular education and training course program and an information system for safety services. The information system was developed in order to improve both the information flux between the national centre for avalanche forecasting, the Swiss Federal Institute for Snow and Avalanche Research SLF, and the local safety services on the one hand and the communication between avalanche safety services in the communities on the other hand. <P style='line-height: 20px;'> The results of this project make a valuable contribution to strengthening organizational measures in avalanche risk management and to closing the gaps, which became apparent during the avalanche winter of 1999. They are not restricted to snow avalanches but can also be adapted for dealing with other natural hazard processes and catastrophes

The effect of communication between the right and left liver on the outcome of surgical drainage for jaundice due to malignant obstruction at the hilus of the liver

Debate continues regarding the optimal management of irresectable malignant proximal biliary obstruction. Controversy exists concerning the ability of unilateral drainage to provide adequate biliary decompression with tumors that have occluded the communication between the right and left hepatic ductal systems. Between October 1986 and October 1989, 18 patients with malignant proximal biliary obstruction were treated by an intrahepatic biliary enteric bypass. Patients were divided into two groups based on the presence or absence of a communication between the right and left biliary systems. In Group I (n = 9), there was free communication; and in Group II (n = 9) there was no communication. There were two perioperative deaths (11%) one due to persistent cholangitis and the other to myocardial insufficiency both with one death in each group. The median survival (excluding perioperative deaths) was 5.6 months. Comparison of pre- and postoperative serum levels of bilirubin and alkaline phosphatase showed a significant decrease in each group, but no difference between the groups in the size of the reduction. Sixteen patients survived at least three months and the palliation was judged as excellent in eight, fair in five, and unchanged in three. These results demonstrate the effectiveness of biliary enteric bypass regardless of communication between the left and right biliary ductal systems.H. U. Baer, M. Rhyner, S. C. Stain, P. W. Glauser, A. R. Dennison, G. J. Maddern, and L. H. Blumgar

What static and dynamic properties should slalom skis possess? Judgments by advanced and expert skiers

Flexural and torsional rigidity are important properties of skis. However, the flexural and torsional rigidity that lead to optimal performance remain to be established. In the present study, four pairs of slalom skis that differed in flexural and torsional rigidity were tested by advanced and expert skiers. Using a 10-item questionnaire, different aspects of the skis’ performance were rated on a 9-point scale. For each pair of skis, physical measurements were compared with the ratings of the two groups of skiers. Correlations (Spearman) were then determined between (i) different mechanical properties of the skis (static and dynamic), (ii) subjective assessments of the participants, and (iii) properties of the skis and the participants’ assessments. The latter showed that expert skiers rate the aspects of the skis more accurately than advanced skiers. Importantly, expert skiers are particularly sensitive to torsion of the skis. These results suggest that such highly rated elements should be addressed in future ski designs

GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells.

Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-beta-mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy

State‐of‐the‐art in marketed adjuvants and formulations in Allergen Immunotherapy: a position paper of the European Academy of Allergy and Clinical Immunology (EAACI)

Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper we summarize current unmet needs of adjuvants in AIT citing current evidence. Four adjuvants are used in products marketed in Europe: aluminium hydroxide (Al(OH)3) is the most frequently used adjuvant, with microcrystalline tyrosine (MCT), monophosphoryl lipid A (MPLA) and calcium phosphate (CaP) used less frequently. Recent studies on humans, and using mouse models, have characterized in part the mechanisms of action of adjuvants on pre‐existing immune responses. AIT differs from prophylactic vaccines that provoke immunity to infectious agents, as in allergy the patient is pre‐sensitized to the allergen. The intended mode of action of adjuvants is to simultaneously enhance the immunogenicity of the allergen, while precipitating the allergen at the injection site to reduce the risk of anaphylaxis. Contrasting immune effects are seen with different adjuvants. Aluminium hydroxide initially boosts Th2 responses, while the other adjuvants utilised in AIT redirect the Th2 immune response toward Th1 immunity. After varying lengths of time, each of the adjuvants supports tolerance. Further studies of the mechanisms of action of adjuvants may advise shorter treatment periods than the current three‐to‐five‐year regimens, enhancing patient adherence. Improved lead compounds from the adjuvant pipeline are under development and are explored for their capacity to fill this unmet need

Semi-automated Magnetic Bead-Based Antibody Selection from Phage Display Libraries

Phage display of combinatorial antibody libraries is a very efficient method for selecting recombinant antibodies against a wide range of molecules. It has been applied very successfully for the generation of therapeutic antibodies for more than a decade. To increase robustness and reproducibility of the selection procedure, we developed a semi-automated selection method for the generation of recombinant antibodies from phage display libraries. In this procedure, the selection targets are specifically immobilised to magnetic particles which can then by automatically handled by a magnetic particle processor. At present up to 96 samples can be handled simultaneously. Applying the processor allows standardisation of panning parameters such as washing conditions, incubation times, or to perform parallel selections on same targets under different buffer conditions. Additionally, the whole protocol has been streamlined to carry out bead loading, phage selection, phage amplification between selection rounds and magnetic particle ELISA for confirmation of binding activity in microtiter plate formats. Until now, this method has been successfully applied to select antibody fragments against different types of target, such as peptides, recombinant or homologous proteins, or chemical compounds

Component‐resolved microarray analysis of IgE sensitization profiles to Culicoides recombinant allergens in horses with insect bite hypersensitivity

Background: Allergy to bites of blood sucking insects, including biting midges can affect both human and veterinary patients. Horses are often suffering from an IgE‐mediated allergic dermatitis caused by bites of midges (Culicoides spp) . With the aim to improve allergen immunotherapy (AIT) numerous Culicoides allergens have been produced as recombinant (r‐) proteins. This study aims to test a comprehensive panel of differently expressed Culicoides r‐allergens on a cohort of IBH‐affected and control horses using an allergen microarray. Methods: IgE levels to 27 Culicoides r‐allergens, including 8 previously unpublished allergens, of which 11 were expressed in more than one expression system, were determined in sera from 347 horses. ROC analyses were carried out, cut‐offs selected using a specificity of 95% and sero‐positivity rates compared between horses affected with insect bite hypersensitivity (IBH) and control horses. The combination of r‐allergens giving the best performing test was determined using logistic regression analysis. Results: Sero‐positivity was significantly higher in IBH horses compared to controls for 25 r‐allergens. Nine Culicoides r‐allergens were major allergens for IBH with seven of them binding IgE in sera from >70% of the IBH‐affected horses. Combination of these top seven r‐allergens could diagnose >90% of IBH‐affected horses with a specificity of >95%. Correlation between differently expressed r‐allergens was usually high (mean = 0.69, range 0.28‐0.91). Conclusion: This microarray will be a powerful tool for development of component‐resolved, patient‐tailored AIT for IBH and could be useful for the study of allergy to biting midges in humans and other species

Interrater Reliability of NI-RADS on Posttreatment PET/Contrast-enhanced CT Scans in Head and Neck Squamous Cell Carcinoma

Purpose: To evaluate the interrater reliability among radiologists examining posttreatment head and neck squamous cell carcinoma (HNSCC) fluorodeoxyglucose PET/contrast-enhanced CT (CECT) scans using Neck Imaging Reporting and Data System (NI-RADS). Materials and Methods: In this retrospective study, images in 80 patients with HNSCC who underwent posttreatment surveillance PET/CECT and immediate prior comparison CECT or PET/CECT (from June 2014 to July 2016) were uploaded to the American College of Radiology's cloud-based website, Cortex. Eight radiologists from seven institutions with variable NI-RADS experience independently evaluated each case and assigned an appropriate prose description and NI-RADS category for the primary site and the neck site. Five of these individuals were experienced readers (> 5 years of experience), and three were novices (< 5 years of experience). In total, 640 lexicon-based and NI-RADS categories were assigned to lesions among the 80 included patients by the eight radiologists. Light generalization of Cohen κ for interrater reliability was performed. Results: Of the 80 included patients (mean age, 63 years ± 10 [standard deviation]), there were 58 men (73%); 60 patients had stage IV HNSCC (75%), and the most common tumor location was oropharynx (n = 32; 40%). Light κ for lexicon was 0.30 (95% CI: 0.23, 0.36) at the primary site and 0.31 (95% CI: 0.24, 0.37) at the neck site. Light κ for NI-RADS category was 0.55 (95% CI: 0.46, 0.63) at the primary site and 0.60 (95% CI: 0.48, 0.69) at the neck site. Percent agreement between lexicon and correlative NI-RADS category was 84.4% (540 of 640) at the primary site and 92.6% (593 of 640) at the neck site. There was no significant difference in interobserver agreement among the experienced versus novice raters. Conclusion: Moderate agreement was achieved among eight radiologists using NI-RADS at posttreatment HNSCC surveillance imaging