Triaziflam and Diaminotriazine derivatives affect enantioselectively multiple herbicide target sites.

Enantiomers of triaziflam and structurally related diaminotriazines were synthesized and their herbicidal mode of action was investigated. The compounds caused light and dark-dependent effects in multiple test systems including heterotrophic cleaver and photoautotrophic algal cell suspensions, the Hill reaction of isolated thylakoids and germinating cress seeds. Dose-response experiments revealed that the (S)-enantiomers of the compounds preferentially inhibited photosystem II electron transport (PET) and algae growth with efficacies similar to that of the herbicide atrazine. In contrast, the (R)-enantiomers of the diaminotriazines were up to 100 times more potent inhibitors of growth in cleaver cell suspensions and cress seedlings in the dark than the (S)-enantiomers. The most active compound, the (R)-enantiomer of triaziflam, inhibited shoot and root elongation of cress and maize seedlings at concentrations below 1 microM. The meristematic root tips swelled into a club shape which is typical for the action of mitotic disrupter herbicides and cellulose biosynthesis inhibitors. Microscopic examination using histochemical techniques revealed that triaziflam (R)-enantiomer blocks cell division in maize root tips 4 h after treatment. The chromosomes proceeded to a condensed state of prometaphase but were unable to progress further in the mitotic cycle. Disruption of mitosis was accompanied by a loss of spindle and phragmoplast micotubule arrays. Concomitantly, cortical microtubules decreased which could lead to isodiametric cell growth and consequently to root swelling. In addition, a decline in cellulose deposition in cell walls was found 24 h after treatment. Compared to the (R)-form, triaziflam (S)-enantiomer was clearly less active. The results suggest that triaziflam and related diaminotriazines affect enantioselectively multiple sites of action which include PET inhibitory activity, mitotic disruption by inhibiting microtubule formation and inhibition of cellulose synthesis.

Ear damage caused by leisure noise.

Noise is a health risk. Recent findings suggest that leisure noise is a substantial danger especially to children, teenagers and young adults. Epidemiological studies of teenagers with no occupational noise exposure show an increasing number with a substantial and measurable irreversible inner ear damage. This is basically due to the wide spread exposition to very loud toys (pistols and squibs), crackers and exposure to electronically amplified music, e.g. from personal cassette players (PCP), at discos or concerts etc. Protection against irreversible ear damage by leisure noise has an important impact in preventive medical care. Therefore the general public must be informed that loud leisure activities may cause damage to the ear. In order to protect children, young people and adults, the legislature ought to set limits for sound levels in discos, concert halls and for music equipment and toys by establishing the necessary standards and regulations.

[Hearing loss caused by leisure noise]. / Gehörschäden durch Freizeitlärm.

Although noise in general can induce hearing loss, environmental noise represents an important risk for children, teenagers and young adults. Epidemiological investigations now support the occurrence of an increasing number of irreversible hearing losses in these groups. Major causes of hearing loss are toys (guns), explosives and electroacoustically amplified music delivered by head sets or heard in discotheques and open air concerts. Clinical indications are discussed.

Financing biotechnology projects: lender due diligence requirements and the role of independent technical consultants.

An increasing number of biotechnology projects are being brought to commercialization using conventional structured finance sources, which have traditionally only been available to proven technologies and primary industries. Attracting and securing competitive cost financing from mainstream lenders, however, will require the sponsor of a new technology or process to undergo a greater level of due diligence. The specific areas and intensity of investigation, which are typically required by lenders in order to secure long-term financing for biotechnology-based manufacturing systems, is reviewed. The processes for evaluating the adequacy of prior laboratory testing and pilot plant demonstrations is discussed. Particular emphasis is given to scale-up considerations and the ability of the proposed facility design to accommodate significant modifications, in the event that scale-up problems are encountered.

[Comments on the revision of the Königstein instructional pamphlet]. / Anmerkungen zur Neuauflage des Königsteiner Merkblattes.

The "Königsteiner Merkblatt (juris prudence)" is an instructional booklet of the general association of juris prudence involves accident insurance ("Hauptverband der gewerblichen Berufsgenossenschaften") in Germany. Medico-legal examinations of occupational noise-induced hearing loss are detailed. In contrast to prior editions, the 4th edition of this booklet, published in January 1996, has been extended by the definitions of legal regulations important for the physician in making medical decisions. Also the number of tests recommended for audiological investigation has been extended. The rules for estimating hearing disability and the calculation of individual handicaps have been changed, and the handicaps for complete deafness in one or both ears have been increased to 20% or 80%, respectively. The most important changes and extensions of the new edition are cited and discussed.

[Hearing loss caused by leisure activity-induced noise]. / Schwerhörigkeit durch Freizeitlärm.

The number of persons with hearing disability in most countries is more than 10%. In developing countries of the third world, inflammations are the most important cause of hearing dysfunction, but in more civilized countries, more and more individuals are injured by a noisy environment and by noise that is individually produced. In this way, a great number of young people acquire defects of hearing which are not reparable. As a consequence the German government has tried to control the possible danger to the community from noise and has arranged that exposure to unnecessary noises be reduced by standards and regulation.

Maturational aspects of the human auditory pathway: anatomical and electrophysiological findings.

Anatomical investigations were carried out on 39 human brains ranging in age from the 29th week of development to the 70th year of life. It was demonstrated that myelination, as a prerequisite for functional maturation, takes place during the 1st year of life. Functional maturation was analyzed with electrophysiological techniques. Normal development depends on adequate stimulation during certain sensitive periods in the 1st year of life as well as the continuous use of the central auditory and speech-hearing systems.

Cell movement and shape are non-random and determined by intracellular, oscillatory rotating waves in Dictyostelium amoebae.

We present evidence for a mechanism of eukaryotic cell movement. The pseudopodial dynamics and shape of Dictyostelium discoideum amoebae were investigated using computer-supported video microscopy. An examination of the cell periphery by the novel method of serial circular maps revealed explicit, classical wave patterns, which indicate the existence of intrinsic intracellular oscillations. The patterns are generated by the transit of self-organized, super-positioned, harmonic modes of rotating oscillatory waves (ROWS). These waves are probably associated with the dynamics of intracellular actin polymerisation and depolymerisation. A Karhunen-Loève expansion was conducted on one cell during 10 min of locomotion using points each 10 degrees around the cell's boundary. The results show that only 2-3 modes are necessary to describe the most essential features of cell movement and shape. Based on this analysis, a wave model was developed, which accurately simulates the dynamics of cell movement and shape during this time. The model was tested by reconstructing the cell's dynamical form by means of the Karhunen-Loève transform. No difference was detected between this reconstruction and the actual cell outline. Although cell movement and shape have hitherto been viewed as random, our results demonstrate that ROWS determine the spatio-temporal expression of pseudopodia, and consequently govern cell shape and movement, non-randomly.

The locomotion, shape and pseudopodial dynamics of unstimulated Dictyostelium cells are not random.

The dynamic periphery of unstimulated, preaggregation, hunger-stage Dictyostelium discoideum amoebae was investigated by time-lapse videomicroscopy and digital image processing. Circular maps (i.e. of each of 360 radii around the cell transformed upon Cartesian coordinates) were constructed around the centroid of individual cell images and analysed in time series. This novel technique generated spatiotemporal structures of various degrees of order in the maps, which resemble classical wave interference patterns. The patterns thus demonstrate that cell movement is not random and that cells are intrinsically vibrating bodies, transited by self-organized, superpositioned, harmonic modes of rotating oscillatory waves (ROWS). These waves appear to depend upon spatiotemporal oscillations in the physicochemical reactions associated with actin polymerization, and they govern pseudopodial movements, cell shape and locomotion generally. ROWS in this case are unrelated to the cyclic-AMP-regulated oscillations, which characterize later, aggregative populations of Dictyostelium. However, the exposure of aggregation-stage cells to a pulse of the chemoattractant cyclic-AMP induces a characteristic sequence of changes in the global cellular concentration and spatiotemporal distribution of fibrillar (F-)actin. This reaction begins with what appears to be a phase resetting of ROWS and it may, therefore, underlie the cellular perception of and response to chemotactic signals. We also develop here an analytical mathematical description of ROWS, and use it to simulate cell movements accurately.