Phase I trial of inhaled natural interleukin 2 for treatment of pulmonary malignancy: toxicity, pharmacokinetics, and biological effects

Safety, local and systemic immunomodulation, and tumor response to treatment with aerosolized natural interleukin 2 (nIL-2) applied five times a day were studied in a Phase I trial in 16 patients with pulmonary malignancies refractory to conventional therapy. The toxicity of inhaled nIL-2 was different from that observed after systemic administration. Reversible airway irritation causing a nonproductive cough represented the dose-limiting toxicity. Mild to moderate reduction of the vital capacity and forced expiratory volume (FEV1) with minor effects on relative FEV1, peak expiratory flow, airway resistance, and PaO2 was experienced by individual patients. In 14 patients suffering from pulmonary metastases due to renal cell cancer, one durable complete response, one partial response, and one mixed response were observed. Inhalation of nIL-2 aerosol resulted in a dose-dependent expansion of pulmonary immunocompetent cells in bronchoalveolar lavage fluid. Posttreatment bronchoalveolar lavage showed an activated lymphocyte phenotype with increased HLA-DR expression. The only systemic biological effect detectable in peripheral blood was a marked increase of soluble interleukin 2 receptor serum levels. We conclude that treatment with aerosolized nIL-2 is an effective means for site-specific immunomodulation and deserves further investigation for the treatment of malignant and inflammatory lung disease.     

Inductive proximity sensor with a flat coil and a new differential relaxation oscillator

A high-sensitivity flat-coil inductive proximity sensor microsystem has been realized and successfully tested. The flat coil, made with CMOS-compatible post processes, is connected to a versatile differential relaxation oscillator electronic interface. In this new and simple interface, the excitation, the signal extraction and amplification are assured by only one operational amplifier. Experimental results on the microsystem confirm that large output frequency variations occur when a metallic target approaches the sensor.     

Electroplating of micro-patterned tools via replication of silicone rubber forms

A two-step replication process is described, allowing the non-destructive reproduction of micro-patterned tools. The first step comprises the embedding of the original part into silicone resin, the resin curing, and the separation of the part from the silicone rubber. The outstanding plasticity and the weak adherence of silicone rubber to most substrate materials facilitate retaining the original part. The second replication step, electroforming, requires silicone rubber metallization and contacting. The demonstrated technique is qualified mainly due to successful precautions against replication artifacts, related to silicone rubber deformability.     

CdTe-CdS solar cells — Production in a new baseline and investigation of material properties

In this paper, we describe our new baseline for CSS-CdTe-CdS solar cells on 10 × 10 cm² substrates. The deposition of the p-n junction and all the following steps were performed at the Institut für Festkörperphysik (IFK) in Jena. Using the new baseline, we are already able to produce solar cells with similar properties as commercial ones. In the batch type process, all manufacturing steps can be investigated separately. We employ Rutherford backscattering spectrometry (RBS), X-ray diffraction (XRD) and external quantum efficiency (EQE) measurements to characterise the structure of the bulk materials and interfaces. It is demonstrated that by RBS the front contact becomes accessible for thinned CdTe films. At the back contact, RBS spectra show a tellurium accumulation which is due to etching. This tellurium rich layer is confirmed by XRD with Rietveld refinement. The intermixing at the CdS-CdTe interface caused by the activation step is quantified by a bandgap determination based on EQE measurements. From the bandgap energy of the CdTe_1 − xS_x compound, we calculated the sulphur fraction x at the interface. XRD measurements imply that the activation step induces a (111) texture in CdTe. With regard to an improved manufacturing process, our cells are compared to industrial cells produced by Antec Solar Energy.     

The effects of context on the correspondence between observational ratings and questionnaire reports of hostile behavior: A multitrait, multimethod approach.

Scholars who study close relationships often measure the same concept with both observational ratings and questionnaire items. In studies where this has been done, the correlations between the two measures have often been low, and one reason may be a "context by measurement" confound. Observational ratings are usually based on behaviors during a specific task, whereas most questionnaire responses are based on a broader context such as "during the past month." In 2001, a total of 292 young couples were videotaped during a discussion task and asked to report on their own behavior and that of their partner during the discussion task and during the past month. The data were configured as a multitrait, multimethod matrix, and the magnitudes of the correlations were estimated with confirmatory factor analysis. The resulting correlations between observer ratings and questionnaire reports of hostile behavior during the videotaped discussion were roughly twice the magnitude of the correlations between observer rating and questionnaire reports during the past month. This suggests that the correspondence between behavioral categories and the content of questionnaire items is greater than previous studies have indicated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Zum Einsatz synthetischer Pyrethroide im vorbeugenden Holzschutz

The synthetic pyrethroids fenvalerate and cypermethrine, natural pyrethrum and lindane were investigated as wood preservatives under conditions of application to determine their contribution to indoor pollution. While pyrethrum degraded within 10 days, fenvalerate and cypermethrine showed high stability and long-term remaining in wood and no volatility into gasphase. In contrast to lindane they do not contribute to indoor pollution.     

Changes in RBE of 14-MeV (d + T) neutrons for V79 cells irradiated in air and in a phantom: is RBE enhanced near the surface?

PURPOSE: The relative biological effectiveness (RBE) for inactivation of V79 cells was determined as function of dose at the Heidelberg 14-MeV (d + T) neutron therapy facility after irradiation with single doses in air and at different depths in a therapy phantom. Furthermore, to assess the reproducibility of RBE determinations in different experiments we examined the relationship between the interexperimental variation in radiosensitivity towards neutrons with that towards low LET 60Co photons. METHODS: Clonogenic survival of V79 cells was determined using the colony formation assay. The cells were irradiated in suspension in small volumes (1.2 ml) free in air or at defined positions in the perspex phantom. Neutron doses were in the range, Dt = 0.5-4 Gy. 60Co photons were used as reference radiation. RESULTS: The radiosensitivity towards neutrons varied considerably less between individual experiments than that towards photons and also less than RBE. However, the mean sensitivity of different series was relatively constant. RBE increased with decreasing dose per fraction from RBE = 2.3 at 4 Gy to RBE = 3.1 at 0.5 Gy. No significant difference in RBE could be detected between irradiation at 1.6 cm and 9.4 cm depth in the phantom. However, an approximately 20% higher RBE was found for irradiation free in air compared with inside the phantom. Combining the two effects, irradiation with 0.5 Gy free in air yielded an approximately 40% higher RBE than a dose of 2 Gy inside the phantom. CONCLUSION: The measured values of RBE as function of dose per fraction within the phantom is consistent with the energy of the neutron beam. The increased RBE free in air, however, is greater than expected from microdosimetric parameters of the beam and may be due to slow recoil protons produced by interaction of multiply scattered neutrons or to an increased contribution of alpha particles from C(n, alpha) reactions near the surface. An enhanced RBE in subcutaneous layers of skin combined with an increase in RBE at low doses per fraction outside the target volume could potentially have significant consequences for normal tissue reactions in radiotherapy patients treated with fast neutrons.     

Accumulation of nitrite and sulfite in yeast cells and synergistic depletion of the intracellular ATP content

Summary When nitrite or sulfite are applied to yeast cells below pH 5.0, an enormous intracellular accumulation occurs. It is assumed that nitrite and sulfite penetrate the cell membrane in their undissociated forms as nitrous acid (pK = 3.3) or sulfurous acid (pK =1.8), respectively. Due to the neutral intracellular pH they are trapped inside the cell in their anionic forms, which are impermeable to the cell membrane. It has previously been shown that sulfite causes a rapid depletion of the ATP content of yeast cells [Schimz, K. L. and Holzer, H. (1979) resp. Hinze et al. as above]. Similarly, millimolar concentrations of nitrite decrease the ATP level to less than 10% of the initial value. Nitrite and sulfite in combination deplete the ATP content of yeast cells much stronger than expected for the sum of the separate effects of these compounds (synergistic effect).

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Akkumulation von Nitrit und Sulfit in Hefezellen und synergistischer Abfall des intrazellulären ATP-Gehalts

Zusammenfassung Wenn Hefezellen mit Nitrit oder Sulft bei pH-Werten unter 5,0 inkubiert werden, beobachtet man eine starke intracelluläre Akkumulation von Nitrit, bzw. Sulfit. Es ist anzunehmen, daß Nitrit und Sulfit in ihrer undissoziierten Form als salpetrige Säure (pK=3,3) bzw. schweflige Säure (pK=1,8) penetrieren und dann in den Zellen durch Neutralisation zu den anionischen Formen, die die Zellmembran nicht mehr permeieren können, abgefangen werden. Ähnlich dem früher beschriebenen raschen Abfall des ATP-Gehaltes nach Zusatz von Sulfit in Hefe [Schimz, KL und Holzer H (1979) Arch Microbiol 121:225–229] und in Bakterien [Hinze H, Maier K, Holzer H (1981) Z Lebensm Unters Forsch 172:389-392] verursacht auch Nitrit einen raschen Abfall des ATP-Gehaltes in Hefe auf weniger als 10 % des Anfangswertes. Werden Nitrit und Sulfit in Kombination verabreicht, so beobachtet man einen wesentlich stärkeren Abfall des ATP-Gehaltes als er aus der Summe der Einzeleffekte von Nitrit, bzw. Sulfit zu erwarten wäre (Synergistischer Effekt).