Titins are megadalton-sized filamentous polypeptides of vertebrate striated muscle. The I-band region of titin underlies the myofibrillar passive tension response to stretch. Here, we show how titins with highly diverse I-band structures and elastic properties are expressed from a single gene. The differentially expressed tandem-Ig, PEVK, and N2B spring elements of titin are coded by 158 exons, which are contained within a 106-kb genomic segment and are all subject to tissue-specific skipping events. In ventricular heart muscle, exons 101 kb apart are joined, leading to the exclusion of 155 exons and the expression of a 2.97-MDa cardiac titin N2B isoform. The atria of mammalian hearts also express larger titins by the exclusion of 90 to 100 exons (cardiac N2BA titin with 3.3 MDa). In the soleus and psoas skeletal muscles, different exon-skipping pathways produce titin transcripts that code for 3.7- and 3.35-MDa titin isoforms, respectively. Mechanical and structural studies indicate that the exon-skipping pathways modulate the fractional extensions of the tandem Ig and PEVK segments, thereby influencing myofibrillar elasticity. Within the mammalian heart, expression of different levels of N2B and N2BA titins likely contributes to the elastic diversity of atrial and ventricular myofibrils.

Zusammenfassung. In der Landesanstalt für Arbeitsschutz Nordrhein-Westfalen (LAfA) wurde 1997 die alternierende Telearbeit als Modellprojekt eingeführt. Mit Interviews, Fragebögen und einem Arbeitsplatzanalyseinstrument haben wir die Auswirkungen untersucht. Es zeigte sich, daß die alternierende Telearbeit im wesentlichen positive Wirkungen auf die Arbeitsleistung, -organisation und -zufriedenheit der Mitarbeiter hat. Kritisch sind hingegen einzelne Aspekte der häuslichen Arbeitsplatzgestaltung zu bewerten. Insgesamt stellt die alternierende Telearbeit eine geeignete Arbeitsorganisationsform für die LAfA dar. Es sollten allerdings persönliche, organisatorische und technische Voraussetzungen für eine erfolgreiche dauerhafte Einführung der Telearbeit beachtet werden.

In 1997, the State Institute for Occupational Safety and Health of North Rhine-Westphalia (German acronym LAfA) introduced alternating telework as a pilot project. We evaluated the effects via interviews, questionnaires and an instrument for workplace analysis. We found that alternating telework had a positive effect on job performance,job satisfaction, and work organization. However, the workplace design at home was not always adequate. On the whole, however alternating telework was found to be a suitable way of organizing work at the LAfA. We discuss personal, organizational, and technical prerequisites that have to be observed for a successful permanent introduction of alternating telework.

When given a choice between two otherwise equivalent options — one in which the probability information is stated and another in which it is missing — most people avoid the option with missing probability information (Camerer & Weber, 1992). This robust, frequently replicated tendency is known as the ambiguity effect. It is unclear, however, why the ambiguity effect occurs. Experiments 1 and 2, which separated effects of the comparison process from those related to missing probability information, demonstrate that the ambiguity effect is elicited by missing probabilities rather than by comparison of options. Experiments 3 and 4 test predictions drawn from the literature on behavioral ecology. It is suggested that choices between two options should reflect three parameters: (1) the need of the organism, (2) the mean expected outcome of each option; and (3) the variance associated with each option's outcome. It is hypothesized that unknown probabilities are avoided because they co-occur with high outcome variability. In Experiment 3 it was found that subjects systematically avoid options with high outcome variability regardless of whether probabilities are explicitly stated or not. In Experiment 4, we reversed the ambiguity effect: when participants' need was greater than the known option's expected mean outcome, subjects preferred the ambiguous (high variance) option. From these experiments we conclude that people do not generally avoid ambiguous options. Instead, they take into account expected outcome, outcome variability, and their need in order to arrive at a decision that is most likely to satisfy this need.

The open reading frame (ORF) and the regulated synthesis of the influenza C viral NS1 protein were analyzed in view of viruses possessing different biological activities. We provide evidence for a 246-amino-acid NS1-ORF, encoded by five viral strains and variants. Prokaryotic expression of the prototype NS1-ORF resulted in a product of 27 kDa, confirming the predicted molecular weight. Using an antiserum raised against recombinant NS1 protein, nonstructural proteins of wild-type virus were detected in infected cells for a limited course of time, whereas a persistent virus variant was characterized by a long-term nonstructural gene expression. As examined by infection experiments, the intracellular distribution of nonstructural protein was nuclear and cytoplasmic, whereas in NS1 gene-transfected cells, the cytoplasmic localization occurred in a fine-grained structure, suggesting an analogy to influenza A viral NS1 protein. Concerning persistent infection, NS1 protein species differing in sizes and posttranslational modifications were observed for a persistent virus variant, as particularly illustrated by a high degree of NS1 phosphorylation. Virus reassortant analyses proved the importance of the NS-coding genomic segment: the minimal viral properties required for the establishment of persistence were transferred with this segment to a monoreassortant virus. Thus the influenza C viral NS1 protein is a 246-amino-acid nuclear-cytoplasmic phosphoprotein that can be subject to specific variations being functionally linked to a persistent virus phenotype.

A gene encoding a novel cell wall‐associated protein of Staphylococcus saprophyticus that binds fibronectin and to sheep erythrocytes has been cloned and sequenced. The 4392 bp open reading frame codes for an amino acid sequence that is quite similar to the Atl, an autolysin, of Staphylococcus aureus and to the AtlE of S. epidermidis. The two regions of most pronounced homology code for an N‐acetyl‐muramyl‐L‐alanine amidase and for an endo‐β‐N‐acetyl‐D‐glucosaminidase. The cloned protein lysed cells of S. saprophyticus and Micrococcus luteus exogenously. Subcloning localized the enzymatic activities to the regions of high homology and demonstrated that the interposed sequence is responsible for the adhesive activities. Two allelic replacement mutants were constructed that lacked autolytic activity and adhesive properties. The N‐terminal portion of the protein contains seven highly conserved, contiguous repeats with no similarity to published sequences. It lacks the motifs typical of Gram‐positive surface proteins and shows a different overall organization. This autolysin/adhesin of S. saprophyticus (Aas) appears to represent a new class of staphylococcal adhesins.

Concentrations of antibiotics below the MIC are able to modulate the expression of virulence-associated genes. In this study, the influence of subinhibitory doses of 31 antibiotics on the expression of the gene encoding the staphylococcal alpha-toxin (hla), a major virulence factor of Staphylococcus aureus, was investigated with a novel gene fusion protocol. The most striking observation was a strong induction of hla expression by subinhibitory concentrations of beta-lactams and an almost complete inhibition of alpha-toxin expression by clindamycin. Whereas glycopeptide antibiotics had no effect, the macrolide erythromycin and several aminoglycosides reduced and fluoroquinolones slightly stimulated hla expression. Furthermore, Northern blot analysis of hla mRNA and Western blot (immunoblot) analysis of culture supernatants of both methicillin-sensitive and methicillin-resistant S. aureus strains revealed that methicillin-induced alpha-toxin expression is a common phenomenon of alpha-toxin-producing strains. Some methicillin-resistant S. aureus isolates produced up to 30-fold more alpha-toxin in the presence of 10 microg of methicillin per ml than in its absence. The results indicate that the novel gene fusion technique is a useful tool for studying the modulation of virulence gene expression by antibiotics. Moreover, the results suggest that the effects of certain antibiotics on virulence properties may be relevant for the management of S. aureus infections.

Evidence has accumulated that urokinase-type plasminogen activator (uPA), its inhibitor (PAI-1) and: receptor (uPAR) are involved in tumor invasion and metastasis. We analyzed the DNA sequences encoding these factors to see if they are altered in the ovarian cancer cell lines OV-MZ-6, OV-MZ-19 and OVCAR-3. In the uPA-encoding cDNA derived from OV-MZ-6 cells (but not in the uPA-cDNA from OVCAR-3 and OV-MZ-19), a so-far unknown mutation was identified in codon 121, resulting in a proline to leucine exchange. This exchange creates an AluI restriction site making restriction fragment length polymorphism (RFLP) analyses possible. Previously published PAI-1 sequences pointed to a variation of amino acid 15 of the PAI-1 signal sequence representing either threonine or alanine, which was confirmed in the present study. The uPAR cDNAs of all three cell lines encoded the published wild-type sequence. In order to elucidate the possible role of the Pro121Leu exchange in uPA and the Ala/Thr variants in the signal sequence of PAI-1 in the development and/or progression of human ovarian cancer, we studied the presence of these mutants or variants in a series of 22 ovarian cancer tissues. In addition to the wild-type sequence, the Pro121Leu exchange in the uPA sequence was detected in 10 out of 22 tumor tissues; 11 tumors carried exclusively the Pro121 allele; in one case exclusively the Leu121 allele was detected. In 18/22 tumors, triplet 15 in the signal sequence of PAI-1 encoded alanine, four DNAs contained both the Ala and the Thr allele. Furthermore, we analyzed another known common single-base-pair insertion/deletion polymorphism (ins/del allele) found in the promoter region of the PAI-1 gene and thought to be of functional importance in regulating PAI-1 gene expression. The PAI-1 ins-allele was found in 3/22, the del-allele in 6/22 and both alleles in 13/22 ovarian cancer tissues. In genomic DNA isolated from peripheral blood of 23 healthy donors, we observed similar allele frequencies of the three polymorphisms as found in the 22 ovarian carcinomas. Taken together, these results suggest that the polymorphisms observed in the uPA and PAI-1 genes may not be linked to ovarian cancer*.

In hindsight, people often claim to have known more than they actually did. This finding has been termed hindsight bias. We report two hindsight-bias experiments which yielded converging results with different methods. All participants first estimated numerical values as answers to difficult knowledge questions, were later given the solutions, and were finally asked to recall their first estimates. In an attempt to reduce the typically found bias, the participants of one group in Experiment 1 were informed in advance about the experimental design and the bias phenomenon, while the participants of another group were not. In Experiment 2 all participants received at the end individual feedback about their recall performance and were then subjected to the same experimental procedure again, twice in succession. The amount of hindsight bias, however, remained unaffected by either of these two manipulations. These findings support automatic processes as explanation for the observed bias and dismiss motivational accounts.

A manual non-radioactive DNA sequencing protocol was developed for rapid analysis of variable HIV-1 genomes. Sets of up to ten primers were used in one sequencing reaction. After polyacrylamide gel electrophoresis and blotting onto nylon membranes the individual sequences were detected by hybridization with digoxigenin-labelled oligonucleotides and chemiluminescence. The method is applicable to any sequencing project where numerous variants of DNA fragments of several 1000 bp of length are to be analysed.

If subjects are asked to recollect a former response after having been informed about the correct response, their recollection tends to approach the correct response. This effect has been termedhindsight bias. We studied hindsight bias in an experiment requiring numerical responses to almanac-type questions for physical quantities. We varied (1) the time at which the correct information was provided, (2) the encoding of the original responses by asking/not asking subjects to give a reason for the respective response, and (3) the motivation to recall correctly. We found that hindsight is less biased if reasons are given and if the correct information is provided at an earlier time. Motivation had only interactive effects: (1) With high motivation to recall correctly, the time the correct information was provided had no influence. (2) With reasons given, the variation of motivation showed no effect. These results rule out purely motivational and purely automatic explanations.

Do subjects, in probability revision experiments, generally neglect base rates due to the use of a representativeness heuristic, or does the use of base rates depend on what we call the internal problem representation? In Experiment 1, we used Kahneman and Tversky’s (1973) engineer-lawyer problem, where random sampling of descriptions is crucial to the internal representation of the problem as one in probability revision. If random sampling was performed and observed by the subjects themselves, then their judgments conformed more to Bayesian theory than to the representativeness hypothesis. If random sampling was only verbally asserted, judgments followed the representativeness heuristic. In Experiment 2 we used the soccer problem, which has the same formal structure but which the subjects’ every day experience already represents as a probability revision problem. With this change in content, subjects’ judgments were indistinguishable from Bayesian performance. We conclude that by manipulating presentation and content, one can elicit either base rate neglect or base rate use, as well as points in between. Th is result suggests that representativeness is neither an all-purpose mental strategy nor even a tendency, but rather a function of the content and the presentation of crucial information. From its origins circa 1660 until the mid-nineteenth century, probability theory was closely identifi ed with rational thinking. In Laplace’s famous phrase, probability theory was believed to be “only common sense reduced to calculus” (Laplace, 1814/1951, p. 196). For the classical probabilists, their calculus codifi ed the intuitions of an elite of reasonable men in the face of uncertainty. And if these reasonable intuitions deviated from the laws of probability theory, it was the latter that were cast into doubt. Such discrepancies actually infl uenced the way in which probability theory developed mathematically (Daston, 1980). In the early decades of the nineteenth century, probability theory shifted from being a description of the intuitions of rational individuals to one of the behavior of the irrational masses (Porter, 1986). But in the 1960s and 1970s experimental psychology reestablished the link between probability theory and rational thinking under uncertainty. However, the new alliance diff ered from the old in two important respects. First, it was now probability theory, rather than intuitive judgments, that was the normative standard. Although probabilists have from time to time doubted whether the additivity law holds in all cases (Shafer, 1978), and although there is evidence that diff erent statistical approaches suggest diff erent answers to the same problem (Birnbaum, 1983), psychologists have generally assumed that statistics spoke with one voice—a necessary assumption for the new normative approach. Second, the link between probability theory and human thinking has become the subject of experimental research. First, by using urn-and-balls problems (e.g., Edwards, 1968; Phillips & Edwards, 1966) and then more

The German Unfallversicherungsgesetz (Accident Insurance Law) of 1884 granted annuities to all employees in case of an industrial accident resulting in a partial or permanent disability. The amount of the annuity was to be assessed “according to the remaining working capacity”. The application of this requirement of the law to the loss of one eye influenced the research on monocular depth perception, in particular by providing impetus to research into adaptation to monocularity during the following thirty years. The failure of this research to produce unequivocal results and a decision of the Reichsversicherungsamt (German Insurance Board) restricting its own jurisdiction put an end to this line of research.