Osteopontin in chronic puromycin aminonucleoside nephrosis

Increased expression of osteopontin (OPN) associated with interstitial monocyte infiltration has been demonstrated in the early phase of a variety of experimental renal diseases. Whether these changes occur in the chronic phase of progressive glomerular disease is unknown. Chronic puromycin aminonucleoside nephrosis (PAN) was induced in 16 rats by the injection of a single bolus of PA into the internal jugular vein, which results in a triphasic disease characterized by minimal glomerular change and marked proteinuria, peaking at about 10 to 14 d and subsiding by 28 d, followed by a quiescent 4-wk period of no or minimal proteinuria and then the development of progressive focal glomerulosclerosis (FGS) and increasing proteinuria. Fifteen rats injected similarly with normal saline served as controls. At 11 d after injection, PA rats demonstrated significantly greater urinary protein excretion (P = 0.0107), cortical tubular OPN expression (P = 0.0086), and intraglomerular (P = 0.0009) and interstitial (P = 0.0212) monocyte infiltration than did the controls. At 42 d, no significant differences between the two groups with respect to the above parameters were detected. At 98 d, PA rats had FGS and showed a definite trend to increased proteinuria, cortical tubular OPN, and intraglomerular monocyte infiltration. Although the cortical interstitial monocyte count was not elevated in PA rats compared with controls, there were significantly more monocytes around OPN-positive cortical tubules than around OPN-negative ones (P = 0.0011). Cortical tubular OPN expression correlated well with urinary protein excretion (r = 0.932, P < 0.0001), cortical tubular proliferating cell nuclear antigen (r = 0.796, P < 0.0001), and intraglomerular monocyte count (r = 0.552, P = 0.0013). The results are consistent with a monocyte chemoattractant role for OPN and suggest that OPN is upregulated in the chronic phase of PAN and that this increase in expression is a result of glomerular events.     

Infra-red and Raman spectroscopic study on the thermal stability and high temperature transformation of hydroazafullerene C59HN

Hydroazafullerene C₅₉HN was studied by vibrational infra-red and Raman spectroscopy and its thermal stability was examined. Fingerprints modes were identified and unambiguously differentiate it from bisazafullerene. At 700 K full transformation to bisazafullerene occurred, while an intermediate metastable phase was identified at 540 K showing different spectra where the splitting of most of the lines is strongly reduced.     

Phase-Error Measurement and Compensation in PLL Frequency Synthesizers for FMCW Sensors—I: Context and Application

The synthesis of linear frequency sweeps or chirps is required, among others, in frequency-modulated continuous-wave radar systems for object position estimation. Low phase and frequency errors in sweeps with high bandwidth are a prerequisite for good accuracy and resolution, but, in certain applications where high measurement rates are desired, the additional demand for short sweep cycles has to be met. Transient phenomena in dynamic synthesizers as well as nonlinear system behavior usually cause unknown phase errors in the system output. For the class of phase-locked-loop (PLL)-based frequency synthesizers, a novel output phase-measurement method and dedicated circuitry are proposed that allow significant reduction of phase errors by adaptive input predistortion. The measurement procedure is implemented within the PLL control circuitry and does not require external equipment. The application of this method to PLL system identification and linearization of extremely short frequency sweeps is shown     

T-cell-mediated cytotoxicity against keratinocytes in sulfamethoxazol-induced skin reaction

BACKGROUND: The incidence of skin rashes or erythema multiforme to sulfamethoxazole in exposed patients is about 3%. Among patients with acquired immunodeficiency syndrome the risk is approximately 10 times higher. The pathogenesis of these reactions and the reason for the increased frequency in HIV infections are not understood. OBJECTIVE: To investigate drug specific T-cell-mediated cytotoxicity in sulfamethoxazole- induced skin reactions. METHODS: Specific T-cell lines and T-cell clones generated from a donor who developed a skin rash to sulfamethoxazole were assessed with a standard 4 h 51Cr cytotoxicity assay in the presence or absence of soluble sulfamethoxazole. B lymphoblasts and keratinocytes with and without interferon gamma pretreatment were used as target cells. Selective blockers of FasL/Fas and perforin-mediated killing and immunostaining for perforin were used to evaluate the involvement of the different cytolytic pathways. RESULTS: CD4+ and CD8+ sulfamethoxazole specific T-cell clones showed a drug-specific and MHC-restricted cytotoxicity against autologous B lymphoblasts in the presence of soluble sulfamethoxazole. Keratinocytes, if pretreated with interferon gamma, were specifically killed predominantly by CD4+ T-cell clones. Specific T-cell clones of both CD4+ and CD8+ phenotype showed a strong immunoreactivity for perforin and the cytotoxicity was blocked by concanamycin A which suggests a perforin-mediated killing. CONCLUSION: Perforin-mediated killing of autologous keratinocytes in the presence of soluble sulfamethoxazole by drug-specific CD4+ lymphocytes may be a pathway for generalized drug-induced delayed skin reactions. The requirement of interferon gamma pretreatment of keratinocytes for efficient specific killing might explain the increased frequency of drug allergies in generalized viral infections like HIV, when interferon gamma levels are elevated.     

High quality double wall carbon nanotubes with a defined diameter distribution by chemical vapor deposition from alcohol

We have synthesized double wall carbon nanotubes (DWNTs) with few defects and little amorphous carbon by hot wall chemical vapor deposition (CVD) of alcohol. Catalysts for the DWNT growth were made from cobalt and molybdenum acetates. Scanning electron microscopy, transmission electron microscopy, multi frequency resonance Raman spectroscopy and optical absorption spectroscopy were used for characterization of the product with regard to DWNT yield, the nanotube diameter distribution, defect concentration and amorphous carbon content. Base pressures lower than 1 × 10⁻⁵ mbar in the CVD reactor considerably suppress defects in the DWNTs. Optimized growth conditions for DWNT formation are presented.     

Evolution of Business Documents Based on UN/CEFACT's Core Components

Standardized business documents are a prerequisite for successful information exchange in electronic business transactions. The United Nations Centre for Trade Facilitation and eBusiness (UN/CEFACT) provides a conceptual modeling approach, called Core Components, used by Business Partners (BPs) for defining business document models (BDMs). BDMs are essential for defining service interfaces in service-oriented systems. However, in such a highly dynamic environment with ever-changing market demands, BPs are confronted with the need to revise their BDMs resulting in a multitude of different versions. BPs may dictate the use of new versions of BDMs, but small- and medium-sized enterprises (SMEs) may not always adopt new BDM versions due to the cost and effort involved, inhibiting automated electronic information exchange. In this article, we propose a framework including (i) a classification of the impact of changes in BDMs, (ii) evolution templates for the automated transformation of business documents between different BDM versions, and (iii) mitigation strategies for evolutions where fully-automated and semantic-preserving transformations are not feasible. Having such a framework at hand provides SMEs with a low-cost and light-weight approach for dealing with evolving market requirements and hence evolving business documents. Finally, we analyze the evolution of UN/CEFACT''s Cross Industry Invoice which has been mandated to be used for electronic invoicing within the European Union as well as present a critical discussion of the evolution templates defined.     

A complete strategy for efficient and accurate multibody dynamics of flexible structures with large lap joints considering contact and friction

This paper deals with the dynamics of jointed flexible structures in multibody simulations. Joints are areas where the surfaces of substructures come into contact, for example, screwed or bolted joints. Depending on the spatial distribution of the joint, the overall dynamic behavior can be influenced significantly. Therefore, it is essential to consider the nonlinear contact and friction phenomena over the entire joint. In multibody dynamics, flexible bodies are often treated by the use of reduction methods, such as component mode synthesis (CMS). For jointed flexible structures, it is important to accurately compute the local deformations inside the joint in order to get a realistic representation of the nonlinear contact and friction forces. CMS alone is not suitable for the capture of these local nonlinearities and therefore is extended in this paper with problem-oriented trial vectors. The computation of these trial vectors is based on trial vector derivatives of the CMS reduction base. This paper describes the application of this extended reduction method to general multibody systems, under consideration of the contact and friction forces in the vector of generalized forces and the Jacobian. To ensure accuracy and numerical efficiency, different contact and friction models are investigated and evaluated. The complete strategy is applied to a multibody system containing a multilayered flexible structure. The numerical results confirm that the method leads to accurate results with low computational effort.     

On aspectualizing component models

Server‐side component models such as Enterprise JavaBeans (EJB) add powerful abstractions to the bare ‘business objects’ layer in order to support a clean separation of server‐side application logic from other concerns such as distribution, security, transaction management and persistence. An improved separation of concerns is also the main goal of aspect‐oriented programming (AOP). This paper compares the two approaches and reasons about the possibility of substituting (parts of) component models using AOP mechanisms. We conclude that AOP is a promising approach to eliminate important shortcomings of the container‐based component approach. However, our analysis of concrete aspect‐oriented languages shows that current AOP technology is not yet mature enough to supersede component models. Copyright © 2003 John Wiley & Sons, Ltd.     

Current Status of Long Non-Coding RNAs in Human Cancer with Specific Focus on Colorectal Cancer

The latest investigations of long non-coding RNAs (lncRNAs) have revealed their important role in human cancers. LncRNAs are larger than 200 nucleotides in length and fulfill their cellular purpose without being translated into proteins. Though the molecular functions of some lncRNAs have been elucidated, there is still a high number of lncRNAs with unknown or controversial functions. In this review, we provide an overview of different lncRNAs and their role in human cancers. In particular, we emphasize their importance in tumorigenesis of colorectal cancer, the third most common cancer worldwide.     

Engineering of Saccharomyces cerevisiae for the production of (+)-ambrein

The triterpenoid (+)-ambrein is the major component of ambergris, a coprolite of the sperm whale that can only be rarely found on shores. Upon oxidative degradation of (+)-ambrein, several fragrance molecules are formed, amongst them (−)-ambrox, one of the highest valued compounds in the perfume industry. In order to generate a Saccharomyces cerevisiae whole-cell biocatalyst for the production of (+)-ambrein, intracellular supply of the squalene was enhanced by overexpression of two central enzymes in the mevalonate and sterol biosynthesis pathway, namely the N-terminally truncated 3-hydroxy-3-methylglutaryl-CoA reductase 1 (tHMG) and the squalene synthase (ERG9). In addition, another key enzyme in sterol biosynthesis, squalene epoxidase (ERG1) was inhibited by an experimentally defined amount of the inhibitor terbinafine in order to reduce flux of squalene towards ergosterol biosynthesis while retaining sufficient activity to maintain cell viability and growth. Heterologous expression of a promiscuous variant of Bacillus megaterium tetraprenyl-β-curcumene cyclase (BmeTC-D373C), which has been shown to be able to catalyse the conversion of squalene to 3-deoxyachillol and then further to (+)-ambrein resulted in production of these triterpenoids in S. cerevisiae for the first time. Triterpenoid yields are comparable with the best microbial production chassis described in literature so far, the methylotrophic yeast Pichia pastoris. Consequently, we discuss similarities and differences of these two yeast species when applied for whole-cell (+)-ambrein production.