Transcriptional regulation of prostate kallikrein-like genes by androgen.

Using gene-specific synthetic oligonucleotides the expression and regulation of kallikrein-like genes in the human prostatic cancer cell line LNCaP were studied. Prostate-specific antigen (PSA) and human glandular kallikrein (hGK-1) together constitute a subfamily of serine proteases exclusively produced in the human prostate. RNA analysis revealed that both genes are expressed in LNCaP cells with PSA basal levels being 2-fold higher than hGK-1 levels. Both mRNAs are induced over a period of 24 h in the presence of 3.3 nM of the synthetic androgen mibolerone. Stimulation of PSA RNA is about 5- fold,whereas hGK-1 stimulation is less pronounced. Nuclear run-on analysis revealed that androgen induction of kallikrein-like genes in LNCaP cells is a rapid event (c3 h) occurring at the level of transcription initiation. Treatment of cells with cycloheximide demonstrates that, while PSA/hGK-1 basal transcription strictly depends on continuous protein synthesis, transcriptional induction by androgen does not. This suggests the direct involvement of the androgen receptor in the induction process independent of additional labile protein factors necessary for kallikrein basal transcription. A binding motif is present in the PSA and hGK-1 promoters, closely resembling the consensus sequence for steroidresponsive elements. The androgen antagonist cyproterone acetate was also able to stimulate transcription of kallikrein-like genes in LNCaP cells. In contrast, androgen-dependent transcriptional suppression of the protooncogene c-myc was strongly counteracted by cyproterone acetate. Thus, antiandrogens act differentially on androgen-regulated prostate-specific (PSA, hGK-1) and growthrelated (c-myc) gene expression in LNCaP cells

The amino acid sequence of chicken histone F3

Histone F3 (III) from chicken erythrocytes was isolated by selective extraction from nucleoprotein with ethanolic-HCl and purified by a single gel filtration step. This protein was found to be homogeneous by the following criteria: gel filtration, electrophoretic mobility, N- and C-terminal amino acid residues and amino acid analysis. The primary structure of this histone was established without resorting to the use of overlapping sequences. This has been achieved with specific chemical cleavages rather than enzymatic degradations chosen and applied, first to the original protein chain, and subsequently to the generated polypeptides, to yield sets of not more than 3 peptides in any single cleavage. Their relative position in the protein or polypeptides became evident after comparison of the N- and C-terminal amino acids in the cleavage products and the uncleaved starting material. The simplicity of the peptide mixture after each cleavage, resulting in easy separation of the peptides, together with the highly efficient Edman degradation of automatic sequencing, allowed a rapid and relatively nonlaborious primary structure determination. Finally, the amino acid sequence is compared with those of protamines and other histones. The evolution and the structure of this protein in relation to DNA is briefly considered

Global strategic alliances in scheduled air transport - implications for competition policy

In international aviation, global strategic alliances (GSAs) have in recent years become an important form of cooperation between airlines. This cooperation has hit the antitrust nerve of the European Commission. Initially, the Commission had attempted to constrain both the market share of the major alliances in transatlantic air transport and their access to major European hubs (London and Frankfurt). The airlines maintain that they need alliances as an inevitable means to adapt to the changing environment in increasingly liberalized and globalized air transport markets in order to remain competitive and to fully realize their growth potential. The final verdict by the Commission will be published soon. Though the existing airline alliances are not stable enough to threaten competition and the openness of airline markets on a global scale, certain hubs or even city pairs might be in danger of being dominated by an individual alliance. This is all the more so as alliances in aviation — contrary to, e.g., strategic R&D alliances in manufacturing — are based on cooperating in a core area of the participants' commercial activities, which might end in collusion. On the other hand, alliances may indeed be regarded as an appropriate tool for internationally active firms to remain competitive. For analyzing alliances' impact on competition, networks seem to be more appropriate than city pairs. On the networks level, complementary alliances usually improve overall welfare via lower fares in all submarkets, whereas parallel alliances tend to result in higher prices in the former parallel markets and lower in other markets due to network spillover effects. Since GSAs in aviation are both of a complementary and a parallel nature, no clear-cut a priori position for or against alliances can be maintained based on conventional antitrust reasoning. From the new institutional economics perspective, alliances are ambiguous as well, because this perspective highlights the efficiency objectives of the participating carriers as well as the potential for collusion and opportunistic behavior. Empirical evidence on the market shares and pricing behavior of alliances and their members does not as yet reflect an increasing threat to competition by these forms of cooperation. But it should be noted that alliances appear to be gaining greater stability over time and that the number of independent competitors is shrinking. These independent competitors contribute much to the dynamics of the competitive process. If their vital role for competition were to be restricted, GSAs in airtransport might prove to be detrimental in the long run. The European Commission is right to be on the alert about GSAs having potentially detrimental effects on competition. However, the Commission should avoid overreacting in its zeal to keep markets open (contestable). It should be borne in mind that market access on transatlantic as well as on most other international air transport routes is still governed by the administrative provisions of intergovernmental bilateral agreements and not by market forces. Therefore, the rrtore relevant question for aviation.policy would be whether competition on the North Atlantic routes could be best maintained by scrapping the bilateral agreements and embarking on a truly liberal open skies aviation agreement between the EU, the United States, and other countries. --

Regeneration of Stochastic Processes: An Inverse Method

We propose a novel inverse method that utilizes a set of data to construct a simple equation that governs the stochastic process for which the data have been measured, hence enabling us to reconstruct the stochastic process. As an example, we analyze the stochasticity in the beat-to-beat fluctuations in the heart rates of healthy subjects as well as those with congestive heart failure. The inverse method provides a novel technique for distinguishing the two classes of subjects in terms of a drift and a diffusion coefficients which behave completely differently for the two classes of subjects, hence potentially providing a novel diagnostic tool for distinguishing healthy subjects from those with congestive heart failure, even at the early stages of the disease development.Comment: 5 pages, two columns, 7 figs. to appear, The European Physical Journal B (2006

Sadder but fitter. The evolutionary function of depressive symptoms following fetal loss

A literature review about an evolutionary model of fetal loss depression is presented. This model conceptualizes depression following miscarriage or stillbirth as an evolutionary protective mechanism to avoid further fetal loss. It postulates that depressive symptoms delay the next reproduction and save maternal resources. These symptoms along with hypochondric symptoms of depression which lead to a search for causes and reappraisal of environmental factors, are probably adaptations to causes of further fetal loss (e.g. epidemics, famines, infections, environmental toxins)

Adapted connections on metric contact manifolds

In this paper, we describe the space of adapted connections on a metric contact manifold through the space of their torsion tensors. The torsion tensor is an element of the space of TM-valued two-forms, which splits into various subspaces. We study the parts of the torsion tensor according to this splitting to completely describe the space of adapted connections. We use this description to obtain characterizations of the generalized Tanaka-Webster connection and to describe the Dirac operators of adapted connections.Comment: 25 pages; some remarks added, minor correction

SEMS vs cSEMS in duodenal and small bowel obstruction : high risk of migration in the covered stent group

Aim: To compare clinical success and complications of uncovered self-expanding metal stents (SEMS) vs covered SEMS (cSEMS) in obstruction of the small bowel. Methods: Technical success, complications and outcome of endoscopic SEMS or cSEMS placement in tumor related obstruction of the duodenum or jejunum were retrospectively assessed. The primary end points were rates of stent migration and overgrowth. Secondary end points were the effect of concomitant biliary drainage on migration rate and overall survival. The data was analyzed according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Results: Thirty-two SEMS were implanted in 20 patients. In all patients, endoscopic stent implantation was successful. Stent migration was observed in 9 of 16 cSEMS (56%) in comparison to 0/16 SEMS (0%) implantations (P = 0.002). Stent overgrowth did not significantly differ between the two stent types (SEMS: 3/16, 19%; cSEMS: 2/16, 13%). One cSEMS dislodged and had to be recovered from the jejunum by way of laparotomy. Time until migration between SEMS and cSEMS in patients with and without concomitant biliary stents did not significantly differ (HR = 1.530, 95%CI 0.731-6.306; P = 0.556). The mean follow-up was 57 ± 71 d (range: 1-275 d). Conclusion: SEMS and cSEMS placement is safe in small bowel tumor obstruction. However, cSEMS is accompanied with a high rate of migration in comparison to uncovered SEMS

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