Modulation of the allergic immune response in BALB/c mice by subcutaneous injection of high doses of the dominant T cell epitope from the major birch pollen allergen Bet v 1

Several in vitro and in vivo studies indicate that application of high doses of dominant T cell epitopes can induce a state of antigen-specific non-responsiveness (anergy). In the present study, we developed a murine model of an allergic immune response to Bet v 1, the major birch pollen allergen. Mice were sensitized by injection of rBet v 1 and the allergic state was proven by the presence of allergen-specific IgE and positive immediate-type skin tests to Bet v 1. In epitope mapping experiments, an immunodominant T cell epitope of Bet v 1 in BALB/c mice was identified by the use of overlapping peptides. This peptide (BV 139) was subsequently employed for treatment. Two tolerization protocols were used: in one approach, the peptide was administered to naive mice before immunization (group BV139-S), in the second, already sensitized mice were treated (S-BV139). The results demonstrated that administering high doses of the dominant T cell epitope of Bet v 1 profoundly diminished T cell proliferation to the peptide in the BV139-S group, and to the peptide as well as to the whole protein in the S-BV139 group. Skin test reactivity to Bet v 1 was reduced in the BV139-S group. However, no differences in terms of specific antibody production between treated and untreated mice could be observed. This study provides evidence that administration of dominant T cell epitopes can down-regulate the allergen-specific T cell response. Proceeding on the assumption that the T lymphocyte response to allergens is crucial for the induction and maintenance of the allergic disease, a modulation of the immune response to allergens by treatment with T cell epitope peptides could represent a promising concept for immunotherapy in the future.     

Correlation between ear canal resonance and tympanic membrane impedance in relation to age and body mass and postmortem changes

The human temporal bone preparation is an acknowledged model for research of the physical processes affecting the outer ear canal and eardrum. Changes affecting the oscillation and resonance behavior of the tympanic membrane and ear canal between death and temporal bone preparation presently exist in only a few studies. Since the influence of age and physique, as well as the width of ear canal on the ear canal resonance may be important, we prepared two separate studies to analyze these questions. The goal of our first test series involved children and was devised to determine if changes in the outer auditory canal resonances differed according to age. In so doing, canal resonance was recorded with a real ear measurement system. Further, we recorded middle ear pressure, impedance of the tympanic membrane, ear canal volume, height, weight and surface of the body, head and ear size. We found a significant decrease in the resonance frequency of the outer ear which was age-dependent and was 2.75 kHz in the 7-year-old child. In a separate study we wanted to know if results found in the postmortem temporal bone reflected in vivo relationships. A tympanometer and real ear measurement system was used to test the resonance behavior of the auditory canal as well as the vibration of the eardrum in dependence on temperature and the time after death for 9 h. We then proved the absence of significant changes in the auditory canal and eardrum oscillation in this time period before possible postmortem changes occurred. Our findings show that the method of bone preservation after its preparation is decisive for the validity of measurements in the isolated human temporal bone.     

Fluorescene in situ hybridization establishes homology between human and silvered leaf monkey chromosomes, reveals reciprocal translocations between chromosomes homologous to human Y/5, 1/9, and 6/16, and delineates an X1X2Y1Y2/X1X1X2X2 sex-chromosome system

The adhesive core of the desmosome is composed of cadherin-like glycoproteins of 2 families, desmocollins and desmogleins. The desmosomal cadherins show distinct patterns of expression in adult epidermis, and we have suggested that the desmocollins have a functional role in regulating the differentiation and/or morphogenesis of that epithelium (North et al. [1996] Proc. Natl. Acad. Sci. USA 93:7701-7705.). To examine this hypothesis, we cloned murine desmocollins and examined the induction patterns of desmocollins 1 and 3 during skin and skin appendage development. Desmocollins 3 and 1 were first expressed in epidermis in highly regional patterns at embryonic days 13.0 and 13.5, respectively, and both were up-regulated in general body epidermis at day 14.5. At this stage, epidermis is undifferentiated and the desmocollins showed an unexpected expression pattern. However, by day 18.5 when skin had undergone terminal differentiation, desmocollin 1 and 3 expression resembled that found in the adult. Thus, the establishment of the adult pattern of desmocollin expression corresponds to the adult pattern of epidermal stratification. We suggest that it is the ratio of desmocollin 1 to desmocollin 3 expression at different levels in the epidermis that is fundamental in establishing this pattern of differentiation.     

Evaluation of the Short Parkinson's Evaluation Scale: a new friendly scale for the evaluation of Parkinson's disease in clinical drug trials

The extensive use of the Unified Parkinson's Disease Rating Scale (UPDRS) has revealed low interrater reliability in some items and redundancy in others. In view of these shortcomings, we have structured a new scale that includes a zero-to three-point scale for each item in the evaluation of PD. The mental axis includes memory, thought disorders, and depression. Activities of daily living (ADL) includes eight items: speech, eating, feeding, dressing, hygiene, handwriting, walking, and turning in bed. The motor examination includes eight items: speech, tremor, rest and posture, rigidity, finger tapping, arising from chair, gait, and postural stability. Complications of therapy were also included: dyskinesias, dystonia, motor fluctuations, and freezing episodes, collected by history. In addition, a global scoring for motor fluctuations that should complement the Hoehn and Yahr Scale was incorporated. In this report, we present a statistical analysis of the ADL, motor evaluation, and complications of therapy sections. Concerning the interrater reliability mean, Kendall's W values were >0.9 for most of the items in the Short Parkinson's Evaluation Scale (SPES). Kendall's W <0.8 (motor evaluation) was found for two items of the SPES and nine items of the UPDRS. The mean interrater reliability for both scales across all seven centers (seven Kendall's W for seven centers) (Mann-Whitney test) showed no statistical differences between the scales. Spearman's correlations between items of both scales were significant. Factor analysis of the SPES and UPDRS data revealed a four-factor solution that explained approximately 60% of the data. All participating centers found the SPES easier to apply and quicker to complete, when compared with the UPDRS. The results obtained strongly favor the introduction of SPES for clinical practice.     

Repetitively pulsed Nd-glass slab lasers

The possibility of obtaining high laser output energies at a 1.32-μm wavelength using thin LiNdLa phosphate glass slabs with a high Nd³⁺ concentration is discussed. In the experiments, 3×14×125-mm slabs were prepared from LiNdLa phosphate glass with a Nd-concentration of 1.2×10²¹ cm^-3. The facets of the slabs were not antireflection-coated. They were tested in a silver-coated quartz tube reflector of 25-mm diameter and pumped by 450-μs pulses from a flash lamp with a 120-mm arc length. In this construction the light, which passes through the slab, returns to it after reflection from the tube surface. Most of the radiation falls on the wider side of the slab at large angles of incidence, thus maximizing its path inside the slab. The quartz reflector was water cooled. The 150-mm laser resonator was formed by two flat mirrors. At 1.32-μm lasing wavelength an output mirror of r=95% reflectivity was used with less than 10% reflectivity at 1.32 μm     

The performance of depressed-cladding single-mode fibers withdifferent b/a ratios

Depressed-cladding single-mode fibers with a first cladding-to-core ratio (b/a) ranging from seven to one and relative refractive-index differences of the core from 0.25 to 0.35% and of the cladding from 0 to -0.2% are investigated experimentally with respect to the LP₁₁ mode cutoff properties, the mode-field diameter, the dispersion, and the bending attenuation. Numerical calculations based on actual profile parameters of the bend loss and the mode-field diameter agree well with experiment. It is demonstrated that low attenuation and bend losses independent of b/a can be obtained if the cutoff wavelength is kept constant by adjusting the core radius, the core index or the index of the first cladding     

Bestimmung der Abtragungsraten von Zirconium,Tantal und der Legierung Tantal-40Niob in fluoridhaltiger azeotroper Salpetersäure mit Hilfe der Radiotracer-Methode

The radiotracer technique as a means to investigate the corrosion of zirconium, tantalum, and a Ta-40Nb alloy in fluoride containing azeotropic nitric acid Zirconium and tantalum as well as the tantalum 40% niobium alloy are of considerable technical importance due to their high corrosion resistance against numerous corrosive media. With respect to corrosion testing in analytically pure azeotropic nitric acid in the temperature range between 20 and 121°C, corrosion rates were determined for zirconium: 7 · 10^?6 to 5 · 10^?4 mm/y, for tantalum: 10^?8 to 4 · 10^?6 mm/y, and for the Ta-40Nb alloy: 2 · 10^?7 to 8 · 10^?6 mm/y [1]. These corrosion rates will be markedly increased by adding small amounts of fluorides or by fluoride impurities. The radiotracer method after neutron activation was applied to determine the corrosion rates in azeotropic fluoride containing nitric acid. Even minute additions of fluorides strongly affect the corrosion resistance of zirconium. In the range between 0.15 and 10 ppm F^? and at a temperature of 108°C, corrosion rates between 5.3 · 10^?3 and 3.1 mm/y were measured. It was impossible to establish a limit for the fluoride concentration, below which the corrosion rate of zirconium will not be adversely influenced. The corrosion rates of tantalum and the Ta-40Nb alloy are considerably increasing above a fluoride concentration of 10 ppm. The highest corrosion rates measured were between 8.4 · 10^?3 mm/y at 50°C/280 ppm F^? and 1.4 · 10^?2 mm/y at 110°C/320 ppm F^?. Within the range of this investigation, the corrosion resistance of tantalum was higher than that of the Ta-40Nb alloy by one order of magnitude. The corrosion resistance of zirconium and tantalum was not influenced by any treatment of the samples before testing.     

A multiple-switch high-voltage DC-DC converter

Series connection of power devices has evolved into a mature technique and is widely applied in HV DC power systems. Static and dynamic voltage balance is ensured by shunting individual devices with dissipative snubbers. The snubber losses become pronounced for increased operating frequencies and adversely affect power density. Capacitive snubbers do not exhibit these disadvantages, but they require a zero-voltage switching mode. Super-resonant power converters facilitate the principle of zero-voltage switching. A high-voltage DC-DC power converter with multiple series-connected devices is proposed. It allows the application of nondissipating snubbers to assist the voltage sharing between the multiple series-connected devices and lowers turnoff losses. Simulation results obtained with a circuit simulator are validated in an experimental power converter operating with two series-connected devices. The behavior of the series connection is examined for MOSFETs and IGBTs by both experimental work with a 2 kW prototype and computer simulation. Applications can be found in traction and heavy industry, where the soft-switching power converter is directly powered from a high-voltage source