Cellular expression of interleukin 2 (IL-2) and its receptor (IL-2R, CD25) in lung tumours

In view of the unclear prognostic and diagnostic role of interleukin 2 (IL-2) and its receptor in human tumours, we examined the cellular expression of IL-2 and of the subunit α of its receptor (IL-2Rα, CD25) in relation to the proliferative activity of various subtypes of lung tumours. The immunocytochemical ABC technique was applied to archival tissue material of neuroendocrine lung tumours: lung carcinoids, including typical carcinoids (TC), atypical carcinoids (AC) and small-cell lung cancers (SCLC) and squamous cell lung cancers (non-small cell lung cancers, NSCLC). Expression of IL-2 was detected in all types of lung tumours. The highest frequency of IL-2 expression (93%) was noted and the most pronounced semi-quantitatively evaluated expression of IL-2 was detected in AC tumour cells. The expression was more pronounced as compared to neoplastic SCLC (p = 0.01) and NSCLC cells (p = 0.005). The results suggest a negative correlation between IL-2 expression and the proliferative activity of tumour cells (evaluated by expression of Ki-67) in AC. The frequency of detection of IL-2 receptor (IL-Rα, CD25) was the highest in NSCLC (94%). Semi-quantitative expression of IL-2R, like that of IL-2, also dominated in the group of atypical lung carcinoids but manifested a significant difference only as compared to typical carcinoids (p = 0.014). Within the groups of tumours studied no correlation could be detected between cellular expressions of IL-2 and IL-2R. Our results demonstrate variable expression of IL-2 and its receptor in various types of lung tumours, but no simple relationship could be detected between tissue expression of the markers and proliferative activity. Appraisal of the diagnostic and/or prognostic significance of the results requires further study

Enamel thickness trends in Plio-Pleistocene hominin mandibular molars

Enamel thickness continues to be an important morphological character in hominin systematics and is frequently invoked in dietary reconstructions of Plio-Pleistocene hominin taxa. However, to date, the majority of published data on molar enamel thickness of Pliocene and early Pleistocene hominins derive from naturally fractured random surfaces of a small number of specimens. In this study we systematically analyze enamel thickness in a large sample of Plio-Pleistocene fossil hominins (n ¼ 99), extant hominoids (n ¼ 57), and modern humans (n ¼ 30). Based on analysis of 2D mesial planes of section derived from microtomography, we examine both average and relative enamel thickness, and the distribution of enamel across buccal, occlusal, and lingual components of mandibular molars. Our results confirm the trend of increasing enamel thickness during the Pliocene that culminates in the thick enamel of the robust Australopithecus species, and then decreases from early Homo to recent modern humans. All hominin taxa share a regional average enamel thickness pattern of thick occlusal enamel and greater buccal than lingual enamel thickness. Pan is unique in exhibiting the thinnest average enamel thickness in the occlusal basin. Statistical analysis indicates that among Pliocene hominins enamel thickness is a weak taxonomic discriminator. The data underlying these results are included in a table in the Supplementary Online Material

AC losses and critical current density of superconducting GdBa2Cu3O7−x

Energy losses occurring in a cylindrical sample of Gd-Ba-Cu-O, subjected to an external AC magnetic field were examined. The loss dependence on the amplitude of the magnetic induction exhibits two stages of flux penetration into the superconductor. Critical current densitities for both stages of penetration were examined and an explanation for such behaviour is proposed. Support for this point of view is obtained by measurements on pulverized sample material. All measurements were performed at a temperature of 4.2 K and in absence of a background field.\ud \ud Analysis of the data provides two critical current densities: an inter-granular critical current density at weak alternating magnetic fields and an intra-granular critical current density at higher magnetic fields. The intra-granular critical current density is at least two orders of magnitude larger than the inter-granular one

Novel High Frequency Silicon Carbide Static Induction Transistor-Based Test-Bed for the Acquisition of SiC Power Device Reverse Recovery Characteristics

A test system is presented that utilizes a high-frequency Silicon Carbide (SiC) Static Induction Transistor (SIT) in place of the traditional MOSFET to test reverse recovery characteristics for the new class of SiC power diodes. An easily implementable drive circuit is presented that can drive the high-frequency SIT. The SiC SIT is also compared to a commonly used Si MOSFET in the test circuit application

Measurement of Ultraviolet Radiative Heating Augmentation in HIEST Reflected Shock Tunnel

Radiance measurements in air at enthalpies from 8-20 MJkg have been made over a 250mm diameter flat-faced test article in Japan Aerospace Exploration Agency's HIgh-Enthalpy Shock Tunnel (HIEST). Measurements were made in the ultraviolet region (200-400 nm wavelength) in an attempt to resolve the long-standing discrepancy between theoryand measurements of heat flux over a blunt body; this discrepancy is often attributed toradiation. The spectra obtained indicate the presence of atomic iron vapor in the flowfield.At the highest enthalpies, the radiance is at the blackbody limit. An attempt to model theradiance is made by taking a nominal CFD flowfield without any contamination productsand processing it through a line-by-line radiation simulation tool. Iron vapor is introducedinto the shocked gas ahead of the model and radiation computations are repeated; the molefraction of iron vapor is adjusted to match the data. For the higher enthalpy conditions, theradiance was strongly absorbed and it was necessary to adjust the temperature and NOdensity in the freestream to match the signal below 300 nm. Once the observed spectrawere satisfactorily matched, the radiance to the stagnation point was then computed. It isshown that the impurity radiation is sufficiently large to explain the discrepancy

An evaluation of oligonucleotide-based therapeutic strategies for polyQ diseases

<p>Abstract</p> <p>Background</p> <p>RNA interference (RNAi) and antisense strategies provide experimental therapeutic agents for numerous diseases, including polyglutamine (polyQ) disorders caused by CAG repeat expansion. We compared the potential of different oligonucleotide-based strategies for silencing the genes responsible for several polyQ diseases, including Huntington's disease and two spinocerebellar ataxias, type 1 and type 3. The strategies included nonallele-selective gene silencing, gene replacement, allele-selective SNP targeting and CAG repeat targeting.</p> <p>Results</p> <p>Using the patient-derived cell culture models of polyQ diseases, we tested various siRNAs, and antisense reagents and assessed their silencing efficiency and allele selectivity. We showed considerable allele discrimination by several SNP targeting siRNAs based on a weak G-G or G-U pairing with normal allele and strong G-C pairing with mutant allele at the site of RISC-induced cleavage. Among the CAG repeat targeting reagents the strongest allele discrimination is achieved by miRNA-like functioning reagents that bind to their targets and inhibit their translation without substantial target cleavage. Also, morpholino analog performs well in mutant and normal allele discrimination but its efficient delivery to cells at low effective concentration still remains a challenge.</p> <p>Conclusions</p> <p>Using three cellular models of polyQ diseases and the same experimental setup we directly compared the performance of different oligonucleotide-based treatment strategies that are currently under development. Based on the results obtained by us and others we discussed the advantages and drawbacks of these strategies considering them from several different perspectives. The strategy aimed at nonallele-selective inhibiting of causative gene expression by targeting specific sequence of the implicated gene is the easiest to implement but relevant benefits are still uncertain. The gene replacement strategy that combines the nonallele-selective gene silencing with the expression of the exogenous normal allele is a logical extension of the former and it deserves to be explored further. Both allele-selective RNAi approaches challenge cellular RNA interference machinery to show its ability to discriminate between similar sequences differing in either single base substitutions or repeated sequence length. Although both approaches perform well in allele discrimination most of our efforts are focused on repeat targeting due to its potentially higher universality.</p