Niels Møller

Structural and Evolutionary Relationships among Protein Tyrosine Phosphatase Domains

With the current access to the whole genomes of various organisms and the completion of the first draft of the human genome, there is a strong need for a structure-function classification of protein families as an initial step in moving from DNA databases to a comprehensive understanding of human biology. As a result of the explosion in nucleic acid sequence information and the concurrent development of methods for high-throughput functional characterization of gene products, the genomic revolution also promises to provide a new paradigm for drug discovery, enabling the identification of molecular drug targets in a significant number of human diseases. This molecular view of diseases has contributed to the importance of combining primary sequence data with three-dimensional structure and has increased the awareness of computational homology modeling and its potential to elucidate protein function. In particular, when important proteins or novel therapeutic targets are identified—like the family of protein tyrosine phosphatases (PTPs) (reviewed in reference 53)—a structure-function classification of such protein families becomes an invaluable framework for further advances in biomedical science. Here, we present a comparative analysis of the structural relationships among vertebrate PTP domains and provide a comprehensive resource for sequence analysis of phosphotyrosine-specific PTPs.

From Conflict to Shared Development: Social Capital in a Tayloristic Environment

The Danish slaughterhouse industry is known for its Tayloristic organization of work, poor industrial relations with frequent wild cat strikes, and a hazardous work environment. However, a few slaughterhouses show big differences in sickness absenteeism, labour turnover and frequency of strikes. These slaughterhouses were studied in order to understand the latitude for cooperation and improvement of the psychosocial work environment. The results revealed that three out of four slaughterhouses studied have moved from a culture based on conflicts and opposing interests to a culture based on mutual trust and respect, thus developing social capital. Developing trust between production managers and shop stewards was the key to the new situation. This happened without jeopardizing the traditional roles of management representatives and shop stewards. The study indicates that there are possibilities of improvement of working conditions under a Taylorized regime based on collaboration between local management and workers. An important factor explaining the results is the strong position of the workers and their unions in the slaughterhouse sector and the general acceptance of unions in the Danish society.

Residue 182 influences the second step of protein-tyrosine phosphatase-mediated catalysis.

Previous enzyme kinetic and structural studies have revealed a critical role for Asp181 (PTP1B numbering) in PTP (protein-tyrosine phosphatase)-mediated catalysis. In the E-P (phosphoenzyme) formation step, Asp181 functions as a general acid, while in the E-P hydrolysis step it acts as a general base. Most of our understanding of the role of Asp181 is derived from studies with the Yersinia PTP and the mammalian PTP1B, and to some extent also TC (T-cell)-PTP and the related PTPa and PTPe. The neighbouring residue 182 is a phenylalanine in these four mammalian enzymes and a glutamine in Yersinia PTP. Surprisingly, little attention has been paid to the fact that this residue is a histidine in most other mammalian PTPs. Using a reciprocal single-point mutational approach with introduction of His182 in PTP1B and Phe182 in PTPH1, we demonstrate here that His182-PTPs, in comparison with Phe182-PTPs, have significantly decreased kcat values, and to a lesser degree, decreased kcat/Km values. Combined enzyme kinetic, X-ray crystallographic and molecular dynamics studies indicate that the effect of His182 is due to interactions with Asp181 and with Gln262. We conclude that residue 182 can modulate the functionality of both Asp181 and Gln262 and therefore affect the E-P hydrolysis step of PTP-mediated catalysis.

Agreements between Labour Unions and Employers’ Associations as a Strategy for the Prevention of Repetitive Strain Injury

In 1992 the Danish labour unions and employers’ associations entered into an agreement on an action plan against hazardous repetitive work. The ambitious goal of this government-supported plan was to reduce hazardous repetitive work by 50 percent by the year 2000. An assessment of the effect of the plan reveals that in spite of certain shortcomings the plan did bring about a reduction of repetitive work, though the goal of a 50 percent reduction was not accomplished. One may draw the important lesson that agreements between the labour market parties need substantial backing from the authorities in order to be effective; otherwise, both the labour unions and employers’ associations will have dif.culties in enforcing obligations on their members. This is especially the case if companies that are either passive or outright negatively disposed are to be covered as well. But if the three parties cooperate, a strategy based on agreements seems to be a valuable approach to the solution of those working environment problems that are dif.cult to regulate by clear and measurable standards.

Utilization of Research Results by the Employees

In the last 10–15 years there has been a general increase in research on the social implications of introducing new technology at the workplace. In the Scandinavian countries, social scientists have had different strategies for utilizing the results of this research.

Conceptualizing Dynamic Capabilities in Lean Production: What are They and How Do They Develop?

Abstract This article addresses the need for developing long-term learning abilities in Lean production: dynamic capabilities. Despite Lean’s remarkable popularity, implementation efforts often emphasize short-term efficiency over developing dynamic capabilities necessary for long-term success. This article advances the understanding of dynamic capabilities in Lean based on a longitudinal in-depth case study at a manufacturing facility. The article shows that dynamic capabilities develop through the development of an organizational setting for improvement activities, termed the improvement system. The improvement system’s effectiveness is characterized by the coherence between participants, technology, management, and organization, and between the improvement system and the work system.