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We identified putative long terminal repeat- (LTR) retrotransposon sequences among the 50,000 random sequence tags (RSTs) obtained by the Génolevures project from genomic libraries of 13 Hemiascomycetes species. In most cases additional sequencing enabled us to assemble the whole sequences of these retrotransposons. These approaches identified 17 distinct families, 10 of which are defined by full-length elements. We also identified five families of solo LTRs that were not associated with retrotransposons. Ty1-like retrotransposons were found in four of five species that are phylogenetically related to Saccharomyces cerevisiae (S. uvarum, S. exiguus, S. servazzii, and S. kluyveri but notZygosaccharomyces rouxii), and in two of threeKluyveromyces species (K. lactis and K. marxianus but not K. thermotolerans). Only multiply crippled elements could be identified in the K. lactis and S. servazziistrains analyzed, and only solo LTRs could be identified in S. uvarum. Ty4-like elements were only detected in S. uvarum,indicating that these elements appeared recently before speciation of the Saccharomyces sensu stricto species. Ty5-like elements were detected in S. exiguus, Pichia angusta, andDebaryomyces hansenii. A retrotransposon homologous with Tca2 from Candida albicans, an element absent from S. cerevisiae, was detected in the closely related species D. hansenii. A complete Ty3/gypsy element was present inS. exiguus, whereas only partial, often degenerate, sequences resembling this element were found in S. servazzii, Z. rouxii, S. kluyveri, C. tropicalis, and Yarrowica lipolytica. P. farinosa(syn. P. sorbitophila) is currently the only yeast species in which no LTR retrotransposons or remnants have been found. Thorough analysis of protein sequences, structural characteristics of the elements, and phylogenetic relationships deduced from these data allowed us to propose a classification for the Ty1/copiaelements of hemiascomycetous yeasts and a model of LTR-retrotransposon evolution in yeasts.

This article analyses and evaluates all types of active and passive labour market policies which have been pursued in East Germany during its transition from a centrally planned to a market economy. To this end, the article makes full use of the numerous, mostly German studies which have been carried out over the past years and which each mostly analysed only one type of labour market policy. The article shows that several of these labour market policy programmes did not improve the participants' position on the labour market; frequently, they even worsened it. In addition, most types of labour market policies had negative side-effects on non-participating unemployed as well as on regular employees. Based on this outcome, the article also draws fundamental policy conclusions.

Purpose: Topotecan has demonstrated exceptional central nervous system penetration as well as radiosensitizing properties in glioblastoma xenografts [Chastagner et al., Int J Radiat Oncol Biol Phy 50: 777–782, 2001]. This phase I trial was performed to determine the maximum tolerated dose and the recommended dose of topotecan continuous infusion administered together with concomitant radiotherapy in patients with glioblastoma. Patients and methods: A total of 20 patients were treated in this trial. Twenty one day topotecan continuous infusion was escalated from 0.3 mg/m2/d in increments of 0.1 mg/m2/d and cohorts of 3–6 patients until maximum tolerated dose was reached; Three-dimensional (3d) conformal radiotherapy was applied concurrently twice daily with a fraction size of 1.75 Gy up to 57.75 Gy total dose. Three additional cycles of maintenance topotecan chemotherapy were scheduled. Results: Fifty-three courses were performed in 5 dose levels (0.3 mg/m2/d: 12 cycles, 0.4 mg/m2/d: 6 cycles, 0.5 mg/m2/d: 10 cycles, 0.6 mg/m2/d: 6 cycles, 0.7 mg/m2/d: 19 cycles). Maximum tolerated dose was reached at dose level 5 (0.7 mg/m2/d), because 3/7 patients suffered from dose limiting toxicity. These were febrile sinusitis, bacterial sepsis and grade 4 thrombocytopenia. Neutropenia of grade 4 was encountered in 2 cycles (0.5 and 0.7 mg/m2/d). Response data were available in 17 patients, 3 of which (18%) achieved partial remission, 12 (71%) stable disease throughout the observation period and 2 (11%) progressive disease. Conclusion: The recommended dose for further trials will be 0.6 mg/m2/d topotecan administered as 21 days continuous infusion in combination with accelerated 3d conformal radiation.

Ziel der Studie war es, die klinischen Ergebnisse nach stereotaktischer Strahlentherapie (Radiochirurgie und stereotaktischer fraktionierter Strahlentherapie) am adaptierten Linearbeschleuniger bei Patienten mit Hirnmetastasen zu evaluieren. Dabei wurden folgende Parameter untersucht: Tumorkontrolle, Uberlebenszeit und Nebenwirkungen. Die Vor- und Nachteile dieser Behandlungstechnik im Vergleich zu traditionellen Behandlungsmethoden (Operation und Ganzschadelbestrahlung) wurden auf der Basis der Literaturdaten und der eigenen Erfahrung analysiert. Nach Behandlung von 80 Lasionen, mit einer medianen Nachbeobachtungszeit von 13 Monaten, kommt die Studie zu folgendem Ergebnis: Die stereotaktische Strahlentherapie am Linearbeschleuniger stellt eine wichtige Therapieoption in der Behandlung der Hirnmetastasen dar. Gegenuber alleiniger Ganzschadelbestrahlung erreicht die stereotaktische Strahlentherapie eine deutlich hohere Tumorkontrolle bei einem niedrigen Nebenwirkungsrisiko. Die stereotaktische Strahlentherapie hat gegenuber der Operation den Vorteil einer kurzeren Behandlungszeit und einer niedrigeren Morbiditat und Mortalitat.

In order to smooth the transition from a planned to a market economy, labour market policies were applied to an unprecedented extent in East Germany. This paper analyses the effects of these policies. As it turns out, labour market policies not only were largely unsuccessful; in many cases they were even prejudicial to the unemployed as well as to regular employees.

A new upstream activating sequence (UAS) 5"-GGTGGCAAA-3" was detected in the promoters of 27 out of the 33 proteasomal genes and of several genes related to the ubiquitin-proteasomal system of Saccharomyces cerevisiae. The sequence was termed proteasome-associated control element (PACE). Gel retardation assay revealed specific binding of PACE with an extracted protein. The protein (64K) was purified by affinity chromatography and was homogeneous by SDS-PAGE. Microsequencing showed that the protein is Rpn4p. The ability of Rpn4p to activate transcription was demonstrated with constructs containing fragments of the RPN5and CDC48gene promoters and reporter cat. Binding to PACE, Rpn4p may act as a common transcription factor on the proteasomal and proteasome-related genes.

Background: Experimental and clinical studies have shown that a prolonged overall treatment time is associated with a decrease in local tumor control. Methods: In a brief review, the clinical data of radiotherapy with split-course or treatment interruption were collected. Results and Conclusion: There was a detrimental effect of the treatment interruption on overall or disease-specific survival in patients with locally advanced head and neck cancer or non-small-cell lung cancer in particular in patients with good prognostic factors and well to moderate differentiated tumors. Therefore, interruption of radiotherapy in patients with curative treatment should be avoided.

Klinische Prufung einer potentiellen Beziehung zwischen polarographisch gemesener Tumoroxygenierung und p53-Status bei Patienten mit Plattenepithelkarzinomen der Kopf-Hals-Region.

Zusammenfassung Die Sozialpolitik hat sich im Laufe der europäischen Integration zu einem immer bedeutenderen Politikbereich der Europäischen Union entwickelt. Im vorliegenden Aufsatz wird untersucht, ob die sozialpolitischen Maßnahmen der EU tatsächlich dazu beitragen, die Lebenslage der sozial schwächeren Personengruppen in der Gemeinschaft zu verbessern. Es werden alle drei Gebiete der europäischen Sozialpolitik behandelt: die Koordinierung der sozialen Sicherungssysteme der Mitgliedsstaaten, die Harmonisierung der Arbeitsbedingungen sowie die Förderung von Chancengleichheit, sozialer Eingliederung und beruflicher Bildung. Wie die Analyse zeigt, sind die sozialpolitischen Maßnahmen der EU mit einer Vielzahl von Nachteilen verbunden. Insbesondere schaden sie häufig gerade denjenigen Personengruppen, die durch sie eigentlich geschützt und gefordert werden sollen.

PURPOSE The development of objective criteria for selecting patients for seminal vesicle irradiation on radical radiotherapy for prostate cancer will be important for successful planning of 3D conformal radiotherapy. MATERIALS AND METHODS Based on morphometric studies from radical prostatectomy specimens, new imaging modalities with potential in the investigation of patients with gross seminal vesicle involvement and clinical factors with potential in the identification of patients with subclinical disease the development of objective guidelines is possible. RESULTS Clinical tumor stage as determined by digital rectal examination, diagnostic tumor biopsy (Gleason Score), and pretherapy serum prostate-specific antigen value were significant factors for the probability of involvement of seminal vesicles. Studies show that seminal vesicle involvement is unlikely if the PSA is < 4 ng/ml or 4 to 10 ng/ml and Gleason Score < 7 and stage < or = T2b. In contrast, involvement of seminal vesicles is highly likely with levels above 20 ng/ml. In patients with PSA levels between 10 and 20 ng/ml and Gleason Score < 7 ultrasonographic findings with regard to tumor volume and localization will be useful to determine the extent of the target volume. For treatment planning a significant reduction in the volumes of irradiation to the rectum and bladder is evident when seminal vesicles were excluded. CONCLUSION Prospective use of the objective criteria will be useful in the selection of patients for seminal vesicle involvement and should be an integral part in 3D conformal radiotherapy of prostate cancer.

A survey of tRNA genes and retroelements (Ty) in the genome of the yeast Saccharomyces cerevisiae is presented. Aspects of genomic organization and evolution of these genetic entities and their interplay are discussed. Attention is also given to the relationship between tRNA gene multiplicity and codon selection in yeast and the role of Ty elements.

This article studies the effects of venture capital on the performance of the labour market. Using data from a much larger sample of countries than previous papers, it finds more readily available venture capital to favourably affect both the unemployment and the employment rate. The magnitude of the estimated effects is substantial. We control for both endogeneity of venture capital availability and most major determinants of labour market performance. The results are robust to variations in specification.

As demonstrated by the last European Union summit meetings, the heads of government and of state of the EU's member states appear firmly intent on starting the planned monetary union on schedule on 1st January 1999. The statements they make, and also any pamphlets and advertisements published by their governments and the European Commission, tend to concentrate one-sidedly on the purported advantages of monetary union. Nevertheless, in most EU countries plans for monetary union are greeted with scepticism or disapproval by a large section of the general public. There are good reasons for this reaction because, as will be explained below, European Monetary Union is in fact associated with serious economic and political risks.

In the framework of the EC programme for sequencing yeast chromosome XV, we have determined the nucleotide sequence of a 26 kb region. Subsequent analysis revealed 13 non-overlapping open reading frames, three of which correspond to known yeast genes. A pair of tRNA genes associated with remnant Ty elements were localized in this region. From structural parameters and/or similarity searches with entries in the current data libraries, a preliminary functional assessment of several of the putative novel gene products can be made. The gene density in this region amounts to one gene in 2 kb. Protein coding regions occupy 61% of the total DNA sequence. Within the intergenic regions, potential regulatory elements can be predicted. The data obtained here may serve as a basis for a more detailed biochemical analysis of the novel genes. The complete nucleotide sequence of the 26 kb segment as depicted in Figure 1 has been deposited at the EBI data library under Accession Number X91067.

Incompletely synthesized polypeptides in the mitochondrial inner membrane are subject to rapid proteolysis. We demonstrate that Yta10p, a mitochondrial homologue of a conserved family of putative ATPases in Saccharomyces cerevisiae, is essential for this proteolytic process. Yta10p-dependent degradation requires divalent metal ions and the hydrolysis of ATP. Yta 10p is an integral protein of the inner mitochondrial membrane exposing the carboxy terminus to the mitochondrial matrix space. Based on the presence of consensus binding sites for ATP, and for divalent metal ions found in a number of metal dependent endopeptidases, a direct role of Yta10p in the proteolytic breakdown of membrane-associated polypeptides in mitochondria is suggested.

There is accumulating evidence for a large, highly conserved gene family of putative ATPases. We have identified 12 different members of this novel gene family (the YTA family) in yeast and determined the nucleotide sequences of nine of these genes. All of the putative gene products are characterized by the presence of a highly conserved domain of 300 amino acids containing specialized forms of the A and B boxes of ATPases. YTA1, YTA2, YTA3 and YTA5 exhibit significant similarity to proteins involved in human immunodeficiency virus Tat-mediated gene expression but more significantly to subunits of the human 26S proteasome. YTA1 and YTA2 are essential genes in yeast. Remarkably, the cDNA of human TBP-1 can compensate for the loss of YTA1. Preliminary experiments indicate that YTA1 is a component of the 26S protease complex from yeast. Our findings lead us to propose that YTA1, YTA2, YTA3 and YTA5 function as regulatory subunits of the yeast 26S proteasome. YTA10, YTA11 and YTA12 share significant homology with the Escherichia coli FtsH protein, and together with YTA4 and YTA6 may constitute a separate subclass within this family of putative ATPases.

Spheroid control doses (SCD50) were determined for ten human glioma lines after fractionated irradiation under oxic conditions. In addition, SF2 values and colony forming efficiencies (CFE) were measured in a soft agarose clonogenic assay. A significant relationship existed between the SCD50 values and the SF2-CFE data pairs (p = 0.01) but the SCD50 values were higher than expected from the SF2 and CFE values. This comparison shows the influence of environmental factors (different in both model systems) on reproductive tumour cell death after irradiation.

From October 1987 to December 1990 a total of 37 patients with deep seated tumours of the pelvis (n = 34), the abdomen (n = 2), or lower leg (n = 1) were treated with radiotherapy and regional hyperthermia. Hyperthermia was produced by the BSD-1000 system and the annular phased array (AA) applicator usually driven at 60-80 MHz, or the BSD-2000 system and the Sigma-60 (S 60) applicator usually driven at 70-90 MHz. Detailed thermal mapping and temperature analysis was performed on 29 patients. The overall mean maximum, average and minimum temperature observed was 42.9 +/- 2.4 degrees C, 40.9 +/- 1.5 degrees C, and 39.3 +/- 0.9 degrees C for all treatments. The time-averaged tumour temperatures achieved in 20%, 50% and 90% of all measured temperature sites were 41.8 +/- 2.1 degrees C (T20), 40.9 +/- 1.6 degrees C (T50), and 39.9 +/- 1.2 degrees C (T90). In addition, the overall mean maximum, average and minimum temperature measured in normal tissue was 42.4 +/- 1.4 degrees C, 40.6 +/- 1.0 degrees C, and 39.2 +/- 0.9 degrees C. The time averaged normal tissue temperatures achieved in 20%, 50% and 90% of all measured temperature sites were 41.3 +/- 1.1 degrees C, 40.6 +/- 1.1 degrees C, and 39.6 +/- 1.0 degrees C. In 36 assessable patients, the overall objective response rate was 31%: 2 complete responses (CR) and 9 partial responses (PR).

The element; Ty4 is a retrotransposon present in low copy number in the genome of Saccharomyces cerevisiae [Stucka et al., Nucleic Acids Res. 17 (1989) 4993–5001]. We have determined the complete nucleotide sequence of one such element from a particular strain and compared it to the other two elements occurring in this strain. The genomic organization of Ty4 is homologous to that found in other retrotransposons of the Ty1 -copia group. The internal part of the element contains two large open reading frames (TY4A and TY4B) overlapping by 226 bp in a +1 mode. TY4A reveals characteristics of the gag portion of retrotransposons and retroviruses, while TY4B consists of a protease, an integrase, a reverse transcriptase, and an RNase H domain (in that order). Our analyses suggest that only one of these copies might be transpositionally active. Sequence comparisons at the amino acid level show that the domains in Ty4 diverge considerably from those of other retrotransposons. The greatest similarity is seen between the reverse transcriptases (50%), the proteases (40%), and the integrases (30%) of Ty4 Ty 1 2 and copia, respectively, whereas the degree of similarity for all other entities of these elements is much lower. Considering evolutionary aspects of the retrotransposons, we have to conclude that Ty4 has diverged at an early stage from the progenitors of other known retroelements and represents a novel and independent subgroup of the Ty1-copia class of retrotransposons.

We have analysed a region some 30 kb centromere distal form PHO5 on the right arm of yeast chromosome II and determined the nucleotide sequence of a 8.95 kb DNA segment from this region. By this analysis we were able to derive the precise location and the transcriptional orientation of CMD1, ALG1, SSN6 and LYS2. An open reading frame of 2370 bp was locatlized between SSN6 and LYS2, which has recently been identified (Schild et al., 1991) to be the RAD16 gene. The putative gene product, 790 amino acids in length, reveals several interesting freatures. It contains a nuclear target singnature and shares several blocks of similarity with the yeast recombinational repair protein RAD54 and the nuclear factor SNF2 (SW12), which is required for teh transcriptioal activation of a number of yeast genes. The similarity blocks in these three proteins are reminiscent of those found in the helicase superfamily. Furthrmore, RAD16 contains a novel ‘double-finger’ motif, which has been encountered in a variety of proteins from different organisms that are suggested to interact with DNA and are involved in diverse functions including site-specific recombination, DNA repair, and transcriptional regulation. The putative gene product of RAD16 then is the first example of a proteins in which the novel double-finger motif is found to be combined with a poteintial DNA helicase framework.

The cif1 mutation of Saccharomyces cerevisiae (Navon et al., Biochemistry 18, 4487-4499, 1979) causes inability to grow on glucose and absence of catabolite inactivation. We have cloned the CIF1 gene by complementation of function and located it in a 2.75 kb SphI-BstEII fragment situated at ca. 18 kb centromere distal of LYS2 and ca. 80 kb centromere proximal of TYR1 on chromosome II. Southern analysis demonstrated that CIF1 is present in a single copy in the yeast genome. Northern analysis revealed that the corresponding mRNA of 1.8 kb is more abundant in cells grown on galactose than in those grown on glucose. A protein of ca. 54 kDa was predicted from the open reading frame in the sequenced fragment. In strains carrying the cif1 mutation the intracellular concentration of ATP decreased immediately after addition of glucose while the intracellular concentration of cAMP did not increase. cAMP concentration increased in response to galactose or 2,4-dinitrophenol. Disruption of BCY1 or overexpression of CDC25 in a cif1 background did not restore growth on glucose, suggesting that the absence of cAMP signal is not the primary cause of lack of growth on glucose. Complementation tests showed that cif1 is not allelic to fdp1 although the two genes seem to be functionally related.

Blood flow related data obtained in different deep-seated tumors and adjacent normal tissues were analyzed in 28 patients who were treated with combined regional hyperthermia and radiation for recurrent or metastatic tumors. The evaluation of blood flow related data has been made using the thermal clearance/thermal cooling coefficient technique and dynamic computed tomography. With both methods significant differences in global perfusion have been observed between tumor center and tumor periphery, between tumor and normal tissue (deep muscle and fat tissue), and between tumor entities. Washout rates or thermal cooling coefficient values, as well as the enhancement of contrast material over baseline (expressed in delta Hounsfield Units), correlated significantly with the achieved steady state temperatures for different tissue categories (i.e., tumor center, tumor periphery, different tumor entities, normal tissue). Thermal cooling coefficient values higher than 63000-83000 W/m3-K (washout rates higher than 15-20 ml/100 g-min) or values of enhancement of contrast material higher than delta 20-25 HU coincide with a limitation in achieving therapeutic temperatures higher than 40 degrees C.

To monitor in vivo transcription and chromatin structure of yeast tRNA genes, we constructed a synthetic tRNA gene that can be used as a reporter. Constructs in which this synthetic tRNA gene is combined with different flanking regions can be integrated into the genome as single copies. The artificial tRNA gene is tagged by the insertion of an intron-like sequence that cannot be spliced out from the precursor and transcripts can thus be identified and quantitated. By several criteria, the artificial tRNA gene behaves like a resident tRNA gene. By measuring the accessibility towards DNaseI in chromatin, we found that the artificial tRNA gene exhibits the same characteristic pattern as resident tRNA genes. Three DNaseI-sensitive sites across the transcribed part of the gene and the immediate flanking regions reflect the formation of the stable transcription complex; positioned nucleosomes are observed in the upstream flanking region. We are confident that the system we have established will prove useful for studying regulatory aspects of tRNA gene expression as well as aspects of pre-tRNA processing and splicing.

Evaluation of late side effects and biochemical control (bNED) 5 years after three-dimensional radiotherapy with moderate, risk-adapted dose escalation. From 03/1999 to 07/2002, 486 patients have been registered in the prospective Austrian-German multicenter phase II trial (AUGE). 399 (82%) localized prostate cancer patients (T1–3 Nx/N0 M0) were evaluated. The low- and intermediate-risk groups were treated with 70 Gy, the high-risk group with 74 Gy, respectively. Additional hormonal therapy (HT) was recommended for intermediate- and high-risk group patients. Late toxicity (EORTC/RTOG) and bNED (ASTRO and Phoenix) were prospectively assessed. Median follow-up was 65 months. Distribution concerning risk groups (low-, intermediate-, high-risk group) showed 29%, 50% and 21% of patients, respectively. HT was given in 87% of patients. The 5-year actuarial rates of late side effects grade ≥ 2 for 70 Gy/74 Gy were 28%/30% (gastrointestinal; p = 0.73) and 19%/34% (urogenital; p = 0,06). The 5-year actuarial bNED rate stratified by risk groups (low-, intermediate-, high-risk group) was 74%, 66% and 50% (ASTRO), and 81%, 80% and 60% (Phoenix), respectively. Within multivariate analysis T-stage and initial prostate specific antigen were significant factors influencing bNED (ASTRO) whereas Gleason Score and duration of HT were not. Dose escalation within standard three-dimensional conformal radiotherapy (3D-CRT) up to a level of 74 Gy did not result in significantly increased gastrointestinal side effects, whereas urogenital side effects showed an increase close to significance. However, the total number of patients with severe toxicity was low. To achieve high tumor control rates with acceptable treatment-related morbidity, local doses of at least 74 Gy should be considered, in particular for intermediate- or high-risk patients applying 3D-CRT.

Born 1932, I was brought up in Stettin. I was trained as an organic chemist at Cologne University, before I entered the Institute of Genetics there in 1962 to work on tRNA structure and function. From 1967 to my retirement in 1997 I worked at the Adolf-Butenandt-Institute (Munich University) on several aspects of molecular biology of the budding yeast, for example tRNA genes, Ty elements, the yeast genome project, and programmed proteolysis. I include facets of my engagement in national and international organizations.

THR1, the gene from Saccharomyces cerevisiae, encoding homoserine kinase, one of the threonine biosynthetic enzymes, has been cloned by complementation. The nucleotide sequence of a 3.1-kb region carrying this gene reveals an open reading frame of 356 codons, corresponding to about 40 kDa for the encoded protein. The presence of three canonical GCN4 regulatory sequences in the upstream flanking region suggests that the expression of THR1 is under the general amino acid control. In parallel, the enzyme was purified by four consecutive column chromatographies, monitoring homoserine kinase activity. In SDS gel electrophoresis, homoserine kinase migrates like a 40-kDa protein; the native enzyme appears to be a homodimer. The sequence of the first 15 NH2-terminal amino acids, as determined by automated Edman degradation, is in accordance with the amino acid sequence deduced from the nucleotide sequence. Computer-assisted comparison of the yeast enzyme with the corresponding activities from bacterial sources showed that several segments among these proteins are highly conserved. Further more, the observed homology patterns suggest that the ancestral sequences might have been composed from separate (functional) domains. A block of very similar amino acids is found in the homoserine kinases towards the carboxy terminus that is also present in many other proteins involved in threonine (or serine) metabolism: this motif, therefore, may represent the binding site for the hydroxyamino acids. Limited similarity was detected between a motif conserved among the homoserine kinases and consensus sequences found in other mono- or dinucleotide-binding proteins.

Using data from 80 countries, this article analyzes whether Protestant religion affects labor market outcomes. Controlling for the impact of labor market regulations, business regulations, the tax burden, the business cycle, the level of economic development, demographic and geographical conditions, wars, and the transition from planned to market economy as well as unobserved country and year effects, we find that countries in which the largest portion of the population practices Protestant religion have substantially higher labor force participation and employment rates, particularly among women. We obtain the same result for a subgroup of 19 industrial countries for which we have better data to control for the impact of labor market institutions and business cycle fluctuations.

Components of the proteasome-ubiquitin pathway are highly conserved throughout eukaryotic organisms. In S. cerevisiae, the expression of proteasomal genes is subject to concerted control by a transcriptional regulator, Rpn4p, interacting with a highly conserved cis-regulatory element, PACE, located in the upstream regions of these genes. Taking advantage of sequence data accumulated from 15 Hemiascomycetes, we performed an in silico study to address the problem of how this system might have evolved among these species. We found that in all these species the Rpn4p homologues are well conserved in terms of sequence and characteristic domain features. The “PACE patterns” turned out to be nearly identical among the Saccharomyces “sensu stricto” species, whereas in the evolutionary more distant species the putatively functional cis-regulatory motifs revealed deviations from the “canonical” PACE nonamere sequence in one or two nucleotides. Our findings suggest that during evolution of the Hemiascomycetes such slightly divergent ancestral motifs have converged into a unique PACE element for the majority of the proteasomal genes within the most recent species of this class. Likewise, the Rpn4 factors within the most recent species of this class show a higher degree of similarity in sequence than their ancestral counterparts. By contrast, we did not detect PACE-like motifs among the proteasomal genes in other eukaryotes, such as S. pombe, several filamentous fungi, A. thaliana, or humans, leaving the interesting question which type of concerted regulation of the proteasome system has developed in species other than the Hemiascomycetes.

In European Monetary Union (EMU) with its decentralized fiscal policies there is a strong bias towards large chronic budget deficits. Having a common currency implies that a member country running high fiscal deficits does not have to bear the full cost of doing so. In particular, high deficits in an individual member country are unlikely to cause a rise in that country’s interest rates. If interest rates rise, they rise in the whole currency area. Thus each individual member state can shift part of the cost of its own fiscal profligacy on to other member countries. However, large chronic budget deficits and the ensuing rising debt-to-GDP ratios are harmful. They crowd out private investment and thus lower long-term economic growth. Furthermore, sooner or later they may induce governments to put pressure on the European Central Bank (ECB) to permit higher inflation in order to erode the real value of the debt. These adverse effects of national fiscal policies make it necessary to effectively limit budgetary deficits of EMU member states. They are the fundamental justification for the Stability and Growth Pact (‘Stability Pact’ for short).

To evaluate the Vienna Rectoscopy Score (VRS) as a feasible and effective tool for detecting and classifying pathologic changes in the rectal mucosa after radiotherapy (RT) for prostate cancer, and, also, to correlate its findings with the European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) score for late rectal toxicity.A total of 486 patients with localized prostate cancer underwent external-beam RT up to 70 or 74 Gy within an Austrian-German prospective multicenter trial. In 166 patients, voluntary rectal sigmoidoscopy was performed before and at 12 and/or 24 months after RT. Pathologic findings such as telangiectasia, congested mucosa, and ulcers were graded (Grades 0-3) and summarized according to the VRS. Late rectal side effects (EORTC/RTOG) were documented and correlated with the corresponding VRS.Before RT, 99% had a VRS score of 0. The median follow-up was 40 months. Overall, a late rectal side effects grade or score 1-3 was detected in 43% by EORTC/RTOG compared with 68% by VRS (p0.05). Grades 0, 1, 2, and 3 late rectal side effects were found using EORTC/RTOG in 57%, 11%, 28%, and 3%, respectively; the corresponding percentages were 32%, 22%, 32%, and 14% for a VRS of 0, 1, 2, and 3, respectively. A significant coherence between the VRS and EORTC/RTOG was found (p0.01).The VRS is a feasible and effective tool for describing and classifying pathologic findings in the rectal mucosa after RT within a multicenter trial. The VRS and EORTC/RTOG showed a high coherence. However the VRS was significantly more sensitive.

Hayek’s theory of cultural evolution has always generated controversy. Interest in Hayek’s theory, and others’ analysis and criticism of it, has been rising of late. This volume urges a reconsideration of Hayeks’ theory of evolution and aims to explore the relevance of Hayek’s theory for its own sake and for evolutionary economics more generally.

PURPOSE: Patients with localized prostate cancer are treated with 3D radiotherapy using a rectal balloon catheter for internal immobilization of the prostate, thereby reducing the radiation dose to the dorsal rectal wall. The purpose of the study was to investigate clinical feasibility and the influence of acute rectal side effects and pre-existing hemorrhoids on patients' acceptance of the rectal balloon catheter. METHODS AND MATERIALS: 442 patients who underwent primary radiation therapy for localized prostate cancer were included in this prospective Austrian-German multicenter trial. The total radiation dose was either 70 Gy or 74 Gy. Acute rectal side effects were documented using the EORTC/RTOG grading score (European Organisation for Research and Treatment of Cancer/Radiation Therapy 225 Oncology Group) at weeks 2, 4 and 7 of radiation treatment. Within the same time intervals patients were interviewed about their tolerance of the rectal balloon catheter, evaluating five categories of acceptance (1 = no major complaints, 2 = pain at/during application, 3 = signs of blood at the balloon catheter after application but without any pain, 4 = signs of blood at the balloon catheter after application and pain, 5 = balloon application had to be stopped). Voluntary rectoscopy prior to radiotherapy was performed in 310 patients. RESULTS: 429/442 patients (97 %) were treated with the balloon catheter. No major complaints were reported in 79 % of the patients and no acute rectal side effects were seen in 52 % of the patients. Grade 1 side effects were seen in 31 % patients, Grade 2 in 17 % and Grade 3 in 0.5 %. Balloon use had to be stopped in only 4 % of the patients. There was significant correlation between balloon discomfort and rectal side effects (p < 0.01). The presence of hemorrhoids in 36 % patients prior to irradiation had no influence on balloon tolerance. CONCLUSIONS: The rectal balloon can be used in 3D radiotherapy of localized prostate cancer with a high degree of acceptance by the patients. Use of the balloon is safe within daily clinical treatment. Patients reporting acute rectal side effects experienced significantly more balloon discomfort, but the presence of hemorrhoids was not found to influence acceptance of the balloon.

Background and purpose To identify endoscopic pathological findings prior to radiotherapy and a possible correlation with acute or chronic rectal side effects after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Patients and methods Between 03/99 and 07/02, a total of 298 patients, who consented in a voluntary rectoscopy prior to radiotherapy were included into the analysis. Patients were treated with a total dose of either 70 or 74 Gy. Pathological rectoscopic findings like hemorrhoids, polyps or diverticula were documented. Acute and late rectal side effects were scored using the EORTC/RTOG score. Results The most frequent pathological endosopic findings were hemorrhoids (35%), polyps (24%) and diverticula (13%). Rectal toxicity was mostly low to moderate. Grade 0/1 cumulative acute and late rectal side effects were 82 and 84%, grade 2 were 18 and 17%, respectively. We could not identify any correlation between preexisting pathological findings and rectal side effects by statistical analysis. Conclusions There is no evidence that prostate cancer patients presenting with endoscopic verified pathological findings in the rectal mucosa at diagnosis are at an increased risk to develop rectal side effects when treated with 3D-CRT of the prostatic region.

Purpose: Using MRI, residual tumor cannot be differentiated from nonspecific postoperative changes in patients with brain gliomas after surgical resection. The goal of this study was to analyze the value of 123 I-α-methyl-tyrosine-single photon emission CT (IMT-SPECT) in radiotherapy planning of patients with brain gliomas after surgical resection. Methods and Materials: In 66 patients with surgically resected brain gliomas (33 glioblastomas, 20 anaplastic astrocytomas, 7 anaplastic oligodendrogliomas, and 6 low-grade astrocytomas), IMT-SPECT and MRI were performed for radiotherapy planning. On the MRI/IMT-SPECT fusion images, the volume with IMT uptake was compared with the volume of the hyperintensity areas of T 2 -weighted MRI and with the volume of contrast enhancement on T 1 -weighted MRI. The regions with IMT uptake and/or MRI changes (composite Vol-MRI/IMT), regions with overlay of IMT uptake and MRI changes (common Vol-MRI/IMT), area with IMT uptake without MRI changes (increase Vol-MRI/IMT), and area with only MRI changes (Vol-MRI minus IMT) were analyzed separately. The planning target volume and boost volume defined using MRI information alone was compared with the planning target volume and boost volume defined by also using the SPECT information. Results: Focally increased IMT uptake was observed in 25 (38%) of 66 patients, contrast enhancement on MRI was outlined in 59 (89%) of 66 patients, and hyperintensity areas on T 2 -weighted MRI were found in all 66 investigated patients. The mean composite Vol-T 2 /IMT was 73 cm 3 . The relative increase Vol-T 2 /IMT, mean relative common Vol-T 2 /IMT, and mean relative Vol-T 2 minus IMT was 4%, 6%, and 90% of the composite Vol-T 2 /IMT, respectively. The mean composite Vol-T 1 /IMT was 14 cm 3 and the mean relative increase Vol-T 1 /IMT, mean relative common Vol-T 1 /IMT, and mean relative Vol-T 1 minus IMT was 21%, 4%, and 64% of the mean composite Vol-T 1 /IMT, respectively. In 19 (29%) of 66 patients, the focal IMT uptake was located outside the MRI changes. In this subgroup, the mean residual volume defined by focal IMT uptake in MRI/IMT-SPECT images, mean Vol-T 1 , and mean Vol-T 2 was 19 cm 3 , 10 cm 3 , and 70 cm 3 , respectively. The mean relative increase T 2 /IMT was 14% and T 1 /IMT was 61%. In this subgroup, the additional information of SPECT led to an increase in boost volume (mean relative increase BV-IMT) by 20%. Conclusion: In patients with surgically resected brain gliomas, the size and location of residual IMT uptake differs considerably from the abnormalities found on postoperative MRI. Because of the known high specificity of IMT uptake for tumor tissue, the findings on IMT-SPECT may significantly modify the target volumes for radiotherapy planning. This will help to focus the high irradiation dose on the tumor area and to spare normal brain tissue.

In almost all countries, the transition from a centrally planned economy to a market economy caused high unemployment. The governments attempted to ease the changeover to a market economy for the unemployed by introducing several passive and active labour market policies. This paper first points out which effects were to be expected of such policies from the perspective of Austrian Economics. These theoretical hypotheses are then tested empirically. It turns out that the hypotheses deducted from Austrian Economics theory are impressively corroborated by the empirical evidence.Dans presque tous les pays, la transition dune economie centralement planifiee vers une economie de marche ont provoque un chomage eleve. Les gouvernements ont essaye dadoucir la transition vers une economie de marche pour les chomeurs en introduisant plusieurs politiques passives et actives sur le marche du travail. Tout dabord, cet article souligne quels etaient les effets attendus de telles politiques a la lumiere de leconomie autrichienne. Ces hypotheses theoriques sont ensuite testees de maniere empirique. Il en ressort que les hypotheses deduites de la theorie economique autrichienne sont corroborees de maniere significative par les preuves empiriques.

In a systematic approach to the study of Saccharomyces cerevisiae genes of unknown function, 150 deletion mutants were constructed (1 double, 149 single mutants) and phenotypically analysed. Twenty percent of all genes examined were essential. The viable deletion mutants were subjected to 20 different test systems, ranging from high throughput to highly specific test systems. Phenotypes were obtained for two-thirds of the mutants tested. During the course of this investigation, mutants for 26 of the genes were described by others. For 18 of these the reported data were in accordance with our results. Surprisingly, for seven genes, additional, unexpected phenotypes were found in our tests. This suggests that the type of analysis presented here provides a more complete description of gene function.