Allergen-specific immunotherapy of Hymenoptera venom allergy:also a matter of diagnosis

Stings of hymenoptera can induce IgE-mediated hypersensitivity reactions in venom-allergic patients, ranging from local up to severe systemic reactions and even fatal anaphylaxis. Allergic patients' quality of life can be mainly improved by altering their immune response to tolerate the venoms by injecting increasing venom doses over years. This venom-specific immunotherapy is highly effective and well tolerated. However, component-resolved information about the venoms has increased in the last years. This knowledge is not only able to improve diagnostics as basis for an accurate therapy, but was additionally used to create tools which enable the analysis of therapeutic venom extracts on a molecular level. Therefore, during the last decade the detailed knowledge of the allergen composition of hymenoptera venoms has substantially improved diagnosis and therapy of venom allergy. This review focuses on state of the art diagnostic and therapeutic options as well as on novel directions trying to improve therapy

Continuous integral kernels for unbounded Schroedinger semigroups and their spectral projections

By suitably extending a Feynman-Kac formula of Simon [Canadian Math. Soc. Conf. Proc, 28 (2000), 317-321], we study one-parameter semigroups generated by (the negative of) rather general Schroedinger operators, which may be unbounded from below and include a magnetic vector potential. In particular, a common domain of essential self-adjointness for such a semigroup is specified. Moreover, each member of the semigroup is proven to be a maximal Carleman operator with a continuous integral kernel given by a Brownian-bridge expectation. The results are used to show that the spectral projections of the generating Schroedinger operator also act as Carleman operators with continuous integral kernels. Applications to Schroedinger operators with rather general random scalar potentials include a rigorous justification of an integral-kernel representation of their integrated density of states - a relation frequently used in the physics literature on disordered solids.Comment: 41 pages. Final version. Dedicated to Volker Enss on the occasion of his 60th birthda

Recombinant phospholipase A1 (Ves v 1) from yellow jacket venom for improved diagnosis of hymenoptera venom hypersensitivity

<p>Abstract</p> <p>Background</p> <p>Hymenoptera venoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Proper diagnosis of hymenoptera venom allergy using venom extracts is severely affected by molecular cross-reactivities. Although non-glycosylated marker allergens would facilitate the identification of the culprit venom, the major allergen phospholipase A1 (Ves v 1) from yellow jacket venom (YJV) remained unavailable so far.</p> <p>Methods</p> <p>Expression of Ves v 1 as wild type and enzymatically inactivated mutant and Ves v 5 in insect cells yielded soluble proteins that were purified via affinity chromatography. Functionality of the recombinant allergens was assessed by enzymatic and biophysical analyses as well as basophil activation tests. Diagnostic relevance was addressed by ELISA-based analyses of sera of YJV-sensitized patients.</p> <p>Results</p> <p>Both major allergens Ves v 1 and Ves v 5 could be produced in insect cells in secreted soluble form. The recombinant proteins exhibited their particular biochemical and functional characteristics and were capable for activation of human basophils. Assessment of IgE reactivity of sera of YJV-sensitized and double-sensitized patients emphasised the relevance of Ves v 1 in hymenoptera venom allergy. In contrast to the use of singular molecules the combined use of both molecules enabled a reliable assignment of sensitisation to YJV for more than 90% of double-sensitised patients.</p> <p>Conclusions</p> <p>The recombinant availability of Ves v 1 from yellow jacket venom will contribute to a more detailed understanding of the molecular and allergological mechanisms of insect venoms and may provide a valuable tool for diagnostic and therapeutic approaches in hymenoptera venom allergy.</p

Earth observations from DSCOVR EPIC instrument

The National Oceanic and Atmospheric Administration (NOAA) Deep Space Climate Observatory (DSCOVR) spacecraft was launched on 11 February 2015 and in June 2015 achieved its orbit at the first Lagrange point (L1), 1.5 million km from Earth toward the sun. There are two National Aeronautics and Space Administration (NASA) Earth-observing instruments on board: the Earth Polychromatic Imaging Camera (EPIC) and the National Institute of Standards and Technology Advanced Radiometer (NISTAR). The purpose of this paper is to describe various capabilities of the DSCOVR EPIC instrument. EPIC views the entire sunlit Earth from sunrise to sunset at the backscattering direction (scattering angles between 168.5° and 175.5°) with 10 narrowband filters: 317, 325, 340, 388, 443, 552, 680, 688, 764, and 779 nm. We discuss a number of preprocessing steps necessary for EPIC calibration including the geolocation algorithm and the radiometric calibration for each wavelength channel in terms of EPIC counts per second for conversion to reflectance units. The principal EPIC products are total ozone (O3) amount, scene reflectivity, erythemal irradiance, ultraviolet (UV) aerosol properties, sulfur dioxide (SO2) for volcanic eruptions, surface spectral reflectance, vegetation properties, and cloud products including cloud height. Finally, we describe the observation of horizontally oriented ice crystals in clouds and the unexpected use of the O2 B-band absorption for vegetation properties.The NASA GSFC DSCOVR project is funded by NASA Earth Science Division. We gratefully acknowledge the work by S. Taylor and B. Fisher for help with the SO2 retrievals and Marshall Sutton, Carl Hostetter, and the EPIC NISTAR project for help with EPIC data. We also would like to thank the EPIC Cloud Algorithm team, especially Dr. Gala Wind, for the contribution to the EPIC cloud products. (NASA Earth Science Division)Accepted manuscrip

Rigorous Real-Time Feynman Path Integral for Vector Potentials

we will show the existence and uniqueness of a real-time, time-sliced Feynman path integral for quantum systems with vector potential. Our formulation of the path integral will be derived on the $L^2$ transition probability amplitude via improper Riemann integrals. Our formulation will hold for vector potential Hamiltonian for which its potential and vector potential each carries at most a finite number of singularities and discontinuities

Component resolution reveals additional major allergens in patients with honeybee venom allergy

BackgroundDetection of IgE to recombinant Hymenoptera venom allergens has been suggested to improve the diagnostic precision in Hymenoptera venom allergy. However, the frequency of sensitization to the only available recombinant honeybee venom (HBV) allergen, rApi m 1, in patients with HBV allergy is limited, suggesting that additional HBV allergens might be of relevance.ObjectiveWe performed an analysis of sensitization profiles of patients with HBV allergy to a panel of HBV allergens.MethodsDiagnosis of HBV allergy (n = 144) was based on history, skin test results, and allergen-specific IgE levels to HBV. IgE reactivity to 6 HBV allergens devoid of cross-reactive carbohydrate determinants (CCD) was analyzed by ImmunoCAP.ResultsIgE reactivity to rApi m 1, rApi m 2, rApi m 3, nApi m 4, rApi m 5, and rApi m 10 was detected in 72.2%, 47.9%, 50.0%, 22.9%, 58.3%, and 61.8% of the patients with HBV allergy, respectively. Positive results to at least 1 HBV allergen were detected in 94.4%. IgE reactivity to Api m 3, Api m 10, or both was detected in 68.0% and represented the only HBV allergen–specific IgE in 5% of the patients. Limited inhibition of IgE binding by therapeutic HBV and limited induction of Api m 3– and Api m 10–specific IgG4 in patients obtaining immunotherapy supports recent reports on the underrepresentation of these allergens in therapeutic HBV preparations.ConclusionAnalysis of a panel of CCD-free HBV allergens improved diagnostic sensitivity compared with use of rApi m 1 alone, identified additional major allergens, and revealed sensitizations to allergens that have been reported to be absent or underrepresented in therapeutic HBV preparations

Ultrahydrophobe chitosanstabilisierte Composite-Schichten auf Aluminiumwerkstoffen

Selbstreinigende, ultrahydrophobe Oberflächen lassen sich in der Technik vielfältig einsetzen. Das ultrahydrophobe Verhalten beruht einerseits auf einer Rauigkeit im μm-Bereich und andererseits auf der chemischen Zusammensetzung der Oberfläche. Durch den gegebenen Oberflächenaufbau sind derartige Materialien jedoch empfindlich gegen Verschleiß. In diesem Beitrag wird ein Schichtverbund bestehend aus Aluminiumoxid und zwei polymeren Komponenten vorgestellt. Die Aluminiumoxidschicht wird auf dem Wege der anodischen Oxidation erzeugt. Dieses seit langem bekannte Verfahren ermöglicht nicht nur die Oxidation der Aluminiumoberfläche, sondern gestattet es, auch, definierte Oberflächenprofile einzustellen. Durch den gezielten Einbau des hochmolekularen Polymers Chitosan in die mikroprofilierte Aluminiumoxidschicht wurde eine mechanische Stabilisierung der Schicht im Sinne eines anorganisch-organischen Composites erreicht. Außerdem dienten die Amino-Seitengruppen des Chitosans als reaktives Interface für die notwendige chemische Hydrophobierung und als Reaktionszentrum für Vernetzungen, wodurch eine weitere mechanische Stabilisierung bewirkt wird. Der Schichtaufbau hat wesentliche

Effects of Recreational Ski Mountaineering on Cumulative Muscle Fatigue – A Longitudinal Trial

Sport is known to have many positive effects on mental and physical health. High-intensity exercise is considered to decrease muscle strength and induce muscle fatigue, which is associated with a higher risk of injury. In recreational alpine skiers, a decrease of eccentric peak hamstring torque, as an indication of muscle fatigue, occurs even after 1 day of skiing. The popularity of ski mountaineering is increasing enormously, but no studies are available on its effects on muscle strength. Therefore, the present study examined the consequences of ski mountaineering on muscle fatigue of the concentric/eccentric quadriceps and/or hamstrings. In addition, a possible role of myofascial foam rolling in reducing muscle fatigue was evaluated. Fifty recreational ski mountaineers (27 males, 23 females) completed five consecutive tours of ski mountaineering within 1 week. After each day of skiing, participants underwent an isokinetic muscle test assessing the concentric and eccentric muscle strength of both thighs. One group completed an additional session of myofascial foam rolling. Right and left concentric quadriceps peak torque, left hamstrings peak torque, left eccentric quadriceps peak torque, as well as right and left hamstring peak torque, were reduced after a single day of ski mountaineering (p ≤ 0.016 for all). However, no cumulative muscle fatigue was detected and we could not demonstrate any effect of myofascial foam rolling. The results show conclusively that a single day of ski mountaineering leads to a significant decrease of concentric and eccentric quadriceps and hamstring strength. Therefore, in order to improve muscle strength for the ski mountaineering season, a physical training program including concentric and eccentric methods can be recommended

Comprehensive calculations of three--body breakup cross sections

We present in detail a theoretical model for fragmentation reactions of three--body halo nuclei. The different reaction mechanisms corresponding to the different processes are described and discussed. Coulomb and nuclear interactions are simultaneously included and the method is therefore applicable for any target, light, intermediate and heavy. Absolute values of many differential cross sections are then available as function of beam energy and target. We apply the method to fragmentation of $^6$He and $^{11}$Li on C, Cu and Pb. A large variety of observables, cross sections and momentum distributions, are computed. In almost all cases we obtain good agreement with the available experimental data.Comment: 41 pages, 10 figures, to be published in Nucl. Phys.

Hypochromic red cells as a prognostic indicator of survival among patients with systemic sclerosis screened for pulmonary hypertension

BACKGROUND: Patients with systemic sclerosis (SSc) are frequently affected by iron deficiency, particularly those with pulmonary hypertension (PH). The first data indicate the prognostic importance of hypochromic red cells (% HRC) > 2% among patients with PH. Hence, the objective of our study was to investigate the prognostic value of % HRC in SSc patients screened for PH. METHODS: In this retrospective, single-center cohort study, SSc patients with a screening for PH were enrolled. Clinical characteristics and laboratory and pulmonary functional parameters associated with the prognosis of SSc were analyzed using uni- and multivariable analysis. RESULTS: From 280 SSc patients screened, 171 could be included in the analysis having available data of iron metabolism (81% female, 60 ± 13 years of age, 77% limited cutaneous SSc, 65 manifest PH, and 73 pulmonary fibrosis). The patients were followed for 2.4 ± 1.8 (median 2.4) years. HRC > 2% at baseline was significantly associated with worse survival in the uni- (p = 0.018) and multivariable (p = 0.031) analysis independent from the presence of PH or pulmonary parenchymal manifestations. The combination of HRC > 2% and low diffusion capacity for carbon monoxide (DLCO) ≤ 65% predicted was significantly associated with survival (p < 0.0001). CONCLUSION: This is the first study reporting that HRC > 2% is an independent prognostic predictor of mortality and can possibly be used as a biomarker among SSc patients. The combination of HRC > 2% and DLCO ≤ 65% predicted could serve in the risk stratification of SSc patients. Larger studies are required to confirm these findings