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.     

Effect of specimen size and loading conditions on spalling of concrete

Different qualities of concrete have been fire tested using different geometries of the specimens as well as different load levels and load configurations. The main objective with the study was to examine a test methodology consisting of a full‐scale test and different small scale‐tests for determining the probability of spalling and the amount of spalling of fire exposed concrete structures. A reference specimen was defined as a one‐sided fire exposed slab with the dimensions 1800 × 1200 mm² giving an exposed area of 1500 × 1200 mm². A number of concrete qualities with different probabilities for spalling, were tested using the reference specimen. These tests showed that the reference specimens worked well giving the expected test results. Small specimens were manufactured in different shapes with the same concrete as the one used in the reference tests. These small specimens were tested either at the same time as the reference specimens in the large furnace or afterwards on a small‐scale furnace where the fire exposed surface was 450 × 360 mm². The test results clearly show the increased probability and the increased amount of spalling by using external compressive loading. The results also show that by using pre‐stress through bars or wires the load can be lost due to heating of the bars/wires which results in a decreased amount of spalling. The boundary of the specimen also affects the amount of spalling. The spalling around the edges was in all tests less than the spalling on the central parts of the exposed area. It could also be noted that the spalling did not pass completely through any of the specimens. The reason for this is probably that the water/vapour could migrate out from the unexposed surface of the specimen. Copyright © 2006 John Wiley & Sons, Ltd.     

Comparative Judgments as an Alternative to Ratings: Identifying the Scale Origin.

Although comparative judgment methods have a number of distinct advantages over ratings, they share one common problem: On the basis of comparative judgments, it is not possible to recover the origin of item evaluations. One item may be judged more positively than another, but this result does not allow any conclusions about whether either of the items are attractive or unattractive. This article discusses the implications of this limitation for the interpretation of individual differences in comparative judgments. It also presents 3 different methods that may allow determination of the scale origin using a nested model comparison approach. An application illustrates the proposed approach as well as the benefits of determining the scale origin in understanding value judgments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A new environmental friendly method for the preparation of sugar acids via catalytic oxidation on gold catalysts

A novel and efficient way of producing of aldonic acids is reported. The selective catalytic oxidation of monosaccharides (arabinose, ribose, xylose, lyxose, mannose, rhamnose, glucose, galactose, N-acetyl-glucosamine) and disaccharides (lactose, maltose, cellobiose, melibiose) on Au, Pd and Pt catalysts was investigated. By using the gold catalyst, a total selectivity with respect to aldonic acids and a high catalytic activity for all investigated sugars was found. The reaction conditions for the production of maltobionic and lactobionic acids via oxidation on gold catalysts were optimised. A high long-term stability of two different gold catalysts for the oxidation of maltose and lactose, respectively, was found.     

Long-term stability of an Au/Al2O3 catalyst prepared by incipient wetness in continuous-flow glucose oxidation

A 0.3% Au/Al₂O₃ catalyst prepared by the incipient wetness (IW) method was investigated in the continuous-flow liquid-phase glucose oxidation. Therefore, a continuous stirred tank reactor (CSTR) system equipped with an ultrasonic separator was used. The continuous-flow glucose oxidation was carried out at 40 °C, pH 9 and 1 bar oxygen partial pressure. Residence time and glucose concentration were varied. The IW gold catalyst showed very high activity and selectivity to gluconic acid within its 110 days of operation and, thus, an excellent long-term stability. Even after severe microbial contaminations of the catalyst, its activity could be completely restored by in situ regeneration with 2-propanol.     

Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) still remains a difficult to cure malignancy. In recent years, the focus has shifted to lipid metabolism for the treatment of HCC. Very little is known about hepatitis B virus (HBV) and C virus (HCV)-related hepatic lipid disturbances in non-malignant and cancer tissues. The present study showed that triacylglycerol and cholesterol concentrations were similar in tumor adjacent HBV and HCV liver, and were not induced in the HCC tissues. Higher levels of free cholesterol, polyunsaturated phospholipids and diacylglycerol species were noted in non-tumorous HBV compared to HCV liver. Moreover, polyunsaturated phospholipids and diacylglycerols, and ceramides declined in tumors of HBV infected patients. All of these lipids remained unchanged in HCV-related HCC. In HCV tumors, polyunsaturated phosphatidylinositol levels were even induced. There were no associations of these lipid classes in non-tumor tissues with hepatic inflammation and fibrosis scores. Moreover, these lipids did not correlate with tumor grade or T-stage in HCC tissues. Lipid reprogramming of the three analysed HBV/HCV related tumors mostly resembled HBV-HCC. Indeed, lipid composition of non-tumorous HCV tissue, HCV tumors, HBV tumors and HBV/HCV tumors was highly similar. The tumor suppressor protein p53 regulates lipid metabolism. The p53 and p53S392 protein levels were induced in the tumors of HBV, HCV and double infected patients, and this was significant in HBV infection. Negative correlation of tumor p53 protein with free cholesterol indicates a role of p53 in cholesterol metabolism. In summary, the current study suggests that therapeutic strategies to target lipid metabolism in chronic viral hepatitis and associated cancers have to consider disease etiology.     

Characterization and tests of planar Co3O4 model catalysts prepared by chemical vapor deposition

The chemical vapor deposition method was used to deposit thin films of cobalt oxide starting with cobalt (II) acetylacetonate and oxygen. The deposition process was investigated and the obtained films were identified as a cubic spinel-type polycrystalline Co₃O₄ with a crystallite size of 30–40 nm. The coating was carbon-free and the surface oxygen concentration was measured to be 66 at.% with AES analysis. Smooth and highly uniform thin films were deposited on planar stainless steel substrates and subjected to TPR and catalysis tests that show positive correlation. The apparent activation energy of Co₃O₄ reduction to CoO was measured to be (33±5) kJ/mol. The catalytic activity of Co₃O₄ was investigated toward the conversion of both propane and ethanol to carbon dioxide. Though the catalytic action was registered at the same temperature, the deactivation process was seen to be different. The catalytic conversion of ethanol induces a fast deactivation process, which was linked to its high ability to reduce Co₃O₄.     

Influence of the preparation conditions on the properties of gold catalysts for the oxidation of glucose

In this work, two deposition–precipitation methods for the preparation of gold catalysts for glucose oxidation were investigated. Thus far, gold colloids immobilized on carbon have been used for catalytic glucose oxidation, but the long-term stability of these systems was not sufficient. To improve the long-term stability we used the deposition–precipitation methods using NaOH (DP NaOH) or urea (DP urea) as precipitation agents as they were described by Haruta and Dekkers, respectively, using alumina as a support material. With these methods, it was possible to prepare highly active and selective catalysts which showed an excellent long-term stability. DP urea was found to be the preferred method, because in contrast to DP NaOH, no losses of gold occurred during the preparation, and it was possible to adjust various gold contents up to 10 wt% Au.     

PDQ: Parallel Distance Queries for deformable meshes

This paper presents a new algorithm to efficiently maintain Bounding-Volume Hierarchies (BVHs) for fast distance queries with deformable polygon meshes using multi-core architectures. The method involves inflating the bounding volumes in an efficient manner to guarantee the enclosure of the deformable model within the BVH at all times. This is done at low additional computation and memory cost without significantly degrading the quality of the BVH and also in a fashion that allows a simple parallel implementation. Additionally, to facilitate fast queries specifically for deforming meshes, we propose a novel algorithm for the bottom-up construction of BVHs that results in much faster distance queries.