Model Comparison Tests to Determine Data Information Content.

In the context of inverse or parameter estimation problems we demonstrate the use of statistically based model comparison tests in several examples of practical interest. In these examples we are interested in questions related to information content of a particular given data set and whether the data will support a more complicated model to describe it. In the first example we compare fits for several different models to describe simple decay in a size histogram for aggregates in amyloid fibril formation. In a second example we investigate whether the information content in data sets for the pest Lygus hesperus in cotton fields as it is currently collected is sufficient to support a model in which one distinguishes between nymphs and adults. Finally in a third example with data for patients having undergone an organ transplant, we question whether the data content is sufficient to estimate more than 5 of the fundamental parameters in a particular dynamic model.

Low-threshold femtosecond optical parametric oscillator based on chirped-pulse frequency conversion.

We report what is to our knowledge the first demonstration of a femtosecond optical parametric oscillator based on chirped-pulse frequency conversion in a long crystal of aperiodically poled potassium titanyl phosphate. The minimum pump threshold power was 15 mW, and a signal slope efficiency of 35% was achieved. Continuous tuning from 1190 to 1450 nm was obtained for an average pump power of 800 mW.

[Endoprosthetic replacement of the ankle joint]. / Endoprothetik am oberen Sprunggelenk. Indikation, Entwicklung, aktueller Stand und Trends]

Endoprosthetic replacement of the ankle joint is considered to be a modern alternative of the well-tried fusions of the joint. We try to explain indications and limits of alloarthroplasty in comparison to arthrodesis. The recent technical evolution will be presented: starting with the two-component-("first generation") and leading to the three-component ("second generation") designs, Suitable for cemented and cementless implantation as well. Results of three-component endoprostheses in the literature and our own experiences with implants of both generations especially regarding the time of survival will be discussed. Basing on the actual knowledge, we try to deduce a prognosis of the future way of ankle replacement.

p53 represses androgen-induced transactivation of prostate-specific antigen by disrupting hAR amino- to carboxyl-terminal interaction.

Prostate-specific antigen (PSA) is highly overexpressed in prostate cancer. One important regulator of PSA expression is the androgen receptor (AR), the nuclear receptor that mediates the biological actions of androgens. AR is able to up-regulate PSA expression by directly binding and activating the promoter of this gene. We provide evidence here that that this AR activity is repressed by the tumor suppressor protein p53. p53 appears to exert its inhibition of human AR (hAR) by disrupting its amino- to carboxyl-terminal (N-to-C) interaction, which is thought to be responsible for the homodimerization of this receptor. Consistent with this, p53 is also able to block hAR DNA binding in vitro. Our previous data have shown that c-Jun can mediate hAR transactivation, and this appears to result from a positive effect on hAR N-to-C interaction and DNA binding. Interestingly, c-Jun is able to relieve the negative effects of p53 on hAR transactivation, N-to-C interaction, and DNA binding, demonstrating antagonistic activities of these two proteins. Importantly, a p53 mutation found in metastatic prostate cancer severely disrupts the p53 negative activity on hAR, suggesting that the inability of p53 mutants to down-regulate hAR is, in part, responsible for the metastatic phenotype.

Surface membrane-expressed CD40 is present on tumor cells from squamous cell cancer of the head and neck in vitro and in vivo and regulates cell growth in tumor cell lines.

Because regional spread to lymph nodes without systemic spread is a relatively common event in squamous cell cancer of the head and neck (SCCHN), it is possible that lymphoid-related receptors or cytokines might directly impact the growth of these tumors. In the present study, we have shown by flow cytometry and Western blotting that the central lymphoid regulatory molecule, CD40, is expressed on the surface of all seven SCCHN tumor cell lines studied. Tumor cell lines also expressed epidermal growth factor (EGF) receptor, MHC class I, and CD95 (Fas) but did not uniformly express other important lymphoid regulatory molecules such as CD80, CD86, or interleukin (IL) 2 receptor components. CD40 ligation by trimeric CD40 ligand (CD40L) resulted in a 20-45% inhibition of tumor cell growth in three of seven cell lines tested. The cytokines IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-11, and IL-15 neither inhibited nor stimulated growth in any of the cell lines tested. EGF had pleiotropic effects on cell growth; it inhibited growth in two cell lines, stimulated growth in one cell line, and had no effect in four cell lines. When coligation by EGF and CD40L was studied, additive or supra-additive growth inhibition was seen in four cell lines. Three cell lines were unaffected by EGF, CD40, or coligation with both reagents. Examination of tumor tissues from 12 previously untreated patients representing a broad spectrum of patients presenting with SCCHN demonstrated CD40 expression in all 12 tumor specimens. This study supports the notion that CD40 is a regulatory molecule for the growth of SCCHN. The important role of CD40-CD40L interactions in the regulation of immune cells in the lymph node and the unique high-level expression of CD40L by these immune cells lend support to the hypothesis that this ligand/receptor pair is an important mediator of cell growth in SCCHN.

c-Fos dimerization with c-Jun represses c-Jun enhancement of androgen receptor transactivation.

The transcriptional activity of the human androgen receptor (hAR), like other nuclear receptors, is dependent on accessory factors. One such factor is c-Jun, which has been shown to have a selective function of mediating androgen receptor-dependent transactivation. This c-Jun activity is inhibited by c-Fos, another protooncoprotein that can dimerize with c-Jun to form the transcription factor AP-1. Here we show that c-jun mediates hAR-induced transactivation from the promoter of the androgen-regulated gene, human kallikrein-2 (hKLK2), and c-Fos blocks this activity. Using c-Fos truncation mutants and measuring hKLK2-dependent transcription, we have determined that the bZIP region of c-Fos is required and sufficient for inhibiting c-Jun enhancement of hAR transactivation. Further truncation analysis of the bZIP shows that the c-Fos dimerization function, mediated through the leucine zipper, is essential for the negative activity, whereas DNA binding, mediated through the basic region, is dispensable. These results suggest that heterodimerization by c-Fos with c-Jun blocks c-Jun's ability to enhance hAR-induced transactivation.

Venous access devices. Guidelines for home healthcare nurses.

A variety of venous access devices are used in home intravenous therapy. It is important for the home healthcare nurse to know the differences among venous access devices and the specific guidelines for using and maintaining venous access devices.

[Biochemical methods in the assessment of activity in rheumatoid arthritis (author's transl)]. / Biochemische Aktivitätskriterien bei rheumatoider Arthritis (RA).

An investigation was carried out in 120 patients with classical rheumatoid arthritis (RA). Prolylhydroxylase activity was determined in the synovial membrane and serum and compared with the level of collagen-like protein in plasma and the hydroxyproline-creatinine quotient in urine. The data were related to the activity of RA as measured according to Voit and Gamp and also according to Lansbury. Activity was, furthermore, also assessed on the basis of newly defined criteria considering clinical, biochemical and histological findings. Prolylhydroxylase activity was significantly correlated to the activity of the RA assessed according to each of these systems. The significance of the known parameters, collagen-like protein in plasma and hydroxyproline-creatinine quotient in urine were confirmed in this larger series of patients. The positive correlation between prolylhydroxylase activities in the synovial membrane, as well as in serum, and the level of collagen metabolites in plasma and urine corroborated the value of biochemical methods in the assessment of activity of RA in order to undertake differentiated therapy.