[Pathways leading to work--the Hamburg integration specialty service]. / Wege in die Arbeit--Der Integrationsfachdienst Hamburg.

A model project of the Federal Ministry of Labour and Social Affairs, the Hamburg Integrationsfachdienst zur Eingliederung Schwerbehinderter (IFD Hamburg, selective placement and support agency for occupational integration of persons with severe disablement) has been active since 1998 in placing people with sensory or physical handicap in the open labour market, based on cooperative partnership between Adecco Dienstleistungen, a market-oriented temporary staff business, and the vocational retraining centre Berufsförderungswerk Hamburg, provider of training programmes for vocational rehabilitation. The IFD combines social competence with business considerations (counselling employers, clarification of wage subsidies or grants, in-depth job analysis, preliminary selection of suitable job seekers). A proactive customer orientation vis-a-vis the prospective employer is the clear message of the IFD's consultants, which hence acts as a professional staff service for severely disabled job seekers in its dealings with the prospective customers, in their majority company decision-makers from small and medium scale firms. Counselling and support offered to the disabled clients are based on a case-management approach, in partnership with the IFD's principals, i.e., employment office, pension insurance fund, industrial injuries insurance institutes, and sometimes also health insurance funds.

Bivalent inhibition of human beta-tryptase.

BACKGROUND: Human beta-tryptase is a mast cell specific trypsin-like serine protease that is thought to play a key role in the pathogenesis of diverse allergic and inflammatory disorders like asthma and psoriasis. The recently resolved crystal structure revealed that the enzymatically active tetramer consists of four quasi-identical monomers. The spatial display of the four identical active sites represents an ideal basis for the rational design of bivalent inhibitors. RESULTS: Based on modeling experiments homobivalent inhibitors were constructed using (i) 6A,6D-dideoxy-6A,6D-diamino-beta-cyclodextrin as a rigid template to bridge the space between the two pairs of identical active sites and (ii) 3-(aminomethyl)benzene as a headgroup to occupy the arginine/lysine specific S1 subsites. A comparative analysis of the inhibitory potencies of synthetic constructs that differ in size and type of the spacer between headgroup and template revealed that the construct contained two 3-(aminomethyl)benzenesulfonyl-glycine groups linked to the 6A,6D-diamino groups of beta-cyclodextrin as an almost ideal bivalent inhibitor with a cooperativity factor of 1.9 vs. the ideal value of 2. The bivalent binding mode is supported by the inhibitor/tetramer ratio of 2:1 required for inactivation of tryptase and by X-ray analysis of the inhibitor/tryptase complex. CONCLUSION: The results obtained with the rigid cyclodextrin template underlined the importance of a minimal loss of conformational entropy in bivalent binding, but also showed the limitations imposed by such rigid core molecules in terms of optimal occupancy of binding sites and thus of enthalpic strains in bidentate binding modes. The main advantage of bivalent inhibitors is their high selectivity for the target enzyme that can be achieved utilizing the principle of multivalency.

Topological testing of the mechanism of homology search promoted by RecA protein.

To initiate homologous recombination, sequence similarity between two DNA molecules must be searched for and homology recognized. How the search for and recognition of homology occurs remains unproven. We have examined the influences of DNA topology and the polarity of RecA-single-stranded (ss)DNA filaments on the formation of synaptic complexes promoted by RecA. Using two complementary methods and various ssDNA and duplex DNA molecules as substrates, we demonstrate that topological constraints on a small circular RecA-ssDNA filament prevent it from interwinding with its duplex DNA target at the homologous region. We were unable to detect homologous pairing between a circular RecA-ssDNA filament and its relaxed or supercoiled circular duplex DNA targets. However, the formation of synaptic complexes between an invading linear RecA-ssDNA filament and covalently closed circular duplex DNAs is promoted by supercoiling of the duplex DNA. The results imply that a triplex structure formed by non-Watson-Crick hydrogen bonding is unlikely to be an intermediate in homology searching promoted by RecA. Rather, a model in which RecA-mediated homology searching requires unwinding of the duplex DNA coupled with local strand exchange is the likely mechanism. Furthermore, we show that polarity of the invading RecA-ssDNA does not affect its ability to pair and interwind with its circular target duplex DNA.

[Deconvolution of infrared spectra using various milk proteins as an example]. / Deconvolution am Beispiel von Infrarotspektren verschiedener Milcheiweissstoffe.

The theory of deconvolution of infra-red spectra is presented and illustrated using milk protein spectra. The advantage of this method is impressively demonstrated and its relevance for dairy farming shown using a simple example, the cooling of milk.