A total approach in ergonomics is a must to attain humane, competitive and sustainable work systems and products

Globalization brings along complexity, competition and change as anticipated by working in teams, quality enhancement of human resources and a change of mind-set to be more holistic in approaches. Enhancement of expertise, widening of the horizon, developing added values as well as preparedness to carry out management of the future have to be built and developed. Conditioning and customizing programs through formal and informal education and training should also be carried out in bridging existing gaps, filling needs and solving key problems. New proper and appropriate curricula must be developed together with encouraging the change of mind-set. It is essential to attain the highest capabilities to work in a team and to think and act holistically, as well as to enhance human relations capabilities in communicating the research results. By so doing, the gaps between research and implementation and between theory and practice need to be bridged; the felt real needs of the target groups could thus be filled; and the root causes of the problems faced in any activity could be solved in a sustainable manner. In implementation, a SHIP (Systemic, Holistic, Interdisciplinary and Participatory) approach must be conducted for identifying, analyzing and solving the problems so as to attain sustainable results. In defining the technology being used, it must be comprehensively assessed through six criteria so that it can be technically, economically, ergonomically and socio-culturally sound, save energy and preserve the environment. Through this total approach, work organization and work systems and their products are expected to be more humane (healthier, safer, comfortable, efficient), competitive and sustainable, as prerequisites for survival and continual development.     

Assessment of the potential germ cell mutagenicity of industrial and plant protection chemicals as part of an integrated study of genotoxicity in vitro and in vivo

An approach is described that enables the germ cell mutagenicity of chemicals to be assessed as part of an integrated assessment of genotoxic potential. It is recommended, first, that the genotoxicity of a chemical be defined by appropriate studies in vitro. This should involve use of the Salmonella mutation assay and an assay for the induction of chromosomal aberrations, but supplementary assays may be indicated in specific instances. If negative results are obtained from these 2 tests there is no need for the conduct of additional tests. Agents considered to be genotoxic in vitro should then be assessed for genotoxicity to rodents. This will usually involve the conduct of a bone marrow cytogenetic assay, and in the case of negative results, a genotoxicity test in an independent tissue. Agents found to be non-genotoxic in vivo are regarded as having no potential for germ cell mutagenicity. Agents found to be genotoxic in vivo may either be assumed to have potential as germ cell mutagens, or their status in this respect may be defined by appropriate germ cell mutagenicity studies. The basis of the approach, which is supported by the available experimental data, is that germ cell mutagens will be evident as somatic cell genotoxins in vivo, and that these will be detected as genotoxins in vitro given appropriate experimentation. The conduct of appropriate and adequate studies is suggested to be of more value than the conduct of a rigid set of prescribed tests.     

Valoración funcional en la demencia grave

Severe dementia is currently one of the main causes of dependence and is defined as cognitive impairment that interferes with the performance of basic activities of daily living. However, in clinical practice severe dementia is difficult to define.Assessment of the ability to perform activities of daily living is a key factor in patients with severe dementia, since functional impairment is a defining feature. Assessment allows an accurate prognosis to be made and a care plan to be established, as well as the effectiveness of the intervention to be evaluated, when necessary.Functional assessment in dementia is complex, since functional status is the expression of multiple interactions, especially in geriatric patients. Functional status is measured by functional scales. In severe dementia, these scales must evaluate basic activities of daily living in the different types of dementia with high sensitivity to changes and strong discriminatory capacity. They should also be culturally adapted and validated in the community and institutional settings. Consensus should be established on the use of these instruments to allow them to be standardized and their results to be compared.     

Asthma in children--problems in diagnosis

Bronchial asthma in children may be difficult to diagnose. Education of the parents regarding allergic conditions, specifically bronchial asthma, is exceedingly important in order to assure satisfactory treatment and clinical results. Chest symptoms of unexplained origin in early life should immediately arouse suspicion of allergic disease. Other causes of asthmatic symptoms must be borne in mind and excluded before a positive diagnosis of bronchial asthma is established. Of the many factors to be considered in investigating a child with asthma, a comprehensive history is most essential. The climate to which the patient is exposed and the psychic influences must be taken into account. Physical examination, x-ray films and laboratory procedures should be carefully executed. Skin testing, especially with food allergens, should not be relied upon to give all the information in allergic disease. Some form of diet trial, such as elimination diets, should be used if sensitivity to food is suspected.     

Blast crisis in chronic myeloid leukemia

Although the worst prognosis among acute forms of leukemia is persistently attributed to the blast crisis of chronic myeloid leukemia, a therapeutic nihilism seems to us to be unreasonable. Even in the developing stage of a blast crisis we consider an aggressive chemotherapy to be justified particularly in younger patients. In this connection, value and necessity of supporting of therapy are especially emphasized. Remissions can be achieved in about one third of patients during the blast crisis of CML. As in other forms of tumour therapy, the initial status, age, and secondary diseases have to be taken into account and a careful, individual therapy planning has to be made. For the future there is the hope that the increasing possibilities of differentiating blasts will allow more systematic therapeutic conclusions to be made. According to the present knowledge the greatest hopes for achieving long-term remissions or even healings can, in our opinion, be expected by bone-marrow transplantation.     

Safety and economic aspects of continuous mammalian cell culture.

Mammalian cell cultures are the most appropriate host cells for recombinant DNA derived products if complex protein structures have to be synthesized in their native form. Due to their physiological behaviour they grow either adherent or in suspension. For the attachment of adherent cells, microcarriers or wire springs can be applied to increase the internal surface of the bioreactor. Both systems provide a simplified media exchange but, however, show some limitations in scale up. In contrast, suspension culture systems as homogeneous systems independent of any carrier have not shown any limitation in scale up. Because most cell lines which are of commercial interest grow in suspension, this technology is best advanced and used in batch and continuous mode. Although mammalian cell cultures are sensitive to hydrodynamic shear forces, technologies for deep tank production are developed which allow stirrer tip speed of up to 1.5 m s-1 sufficient for oxygen uptake, suspension of cells and homogeneous supply with nutrients. For long term bioprocesses without selection pressure it has to be considered that transformed cell lines might show genetic instability due to their variations of chromosomes. In addition, sterile technology becomes an important factor in long term bioprocesses. The decision as to which cell culture system should be chosen, whether batch or continuous processes should be applied essentially is based on the capital investment, the amount of material to be produced, genetic stability of the production cell line, reliability of sterile technology and the flexibility required in the production plant. Under the assumption that 20 kg of a protein have to be produced per year and the same product concentrations in the harvest fluid are reached in the batch process and for instance in the chemostat, it can be considered that the capital investment for one 10,000 l batch process and a 2 x 2,000 l continuous process, necessary to produce the amount of material, is comparable. Risk of microbial contamination or technical failure can be considered to be fairly low in the batch process. The economic risk for long term bioprocess in the chemostat can be expected to be medium and high in the perfusion system which is in the large scale not technically fully satisfactory. In addition, due to the longer down time period after contaminations and the start up of the continuous process, the annual yield of the batch process can be considered to be higher.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mutants of Arabidopsis lacking starch branching enzyme II substitute plastidial starch synthesis by cytoplasmic maltose accumulation

Three genes, BE1, BE2, and BE3, which potentially encode isoforms of starch branching enzymes, have been found in the genome of Arabidopsis thaliana. Although no impact on starch structure was observed in null be1 mutants, modifications in amylopectin structure analogous to those of other branching enzyme II mutants were detected in be2 and be3. No impact on starch content was found in any of the single mutant lines. Moreover, three double mutant combinations were produced (be1 be2, be1 be3, and be2 be3), and the impact of the mutations on starch content and structure was analyzed. Our results suggest that BE1 has no apparent function for the synthesis of starch in the leaves, as both be1 be2 and be1 be3 double mutants display the same phenotype as be2 and be3 separately. However, starch synthesis was abolished in be2 be3, while high levels of alpha-maltose were assayed in the cytosol. This result indicates that the functions of both BE2 and BE3, which belong to class II starch branching enzymes, are largely redundant in Arabidopsis. Moreover, we demonstrate that maltose accumulation depends on the presence of an active ADP-glucose pyrophosphorylase and that the cytosolic transglucosidase DISPROPORTIONATING ENZYME2, required for maltose metabolization, is specific for beta-maltose.     

Probabilistic computation by neuromine networks

In this paper, we address the question, can biologically feasible neural nets compute more than can be computed by deterministic polynomial time algorithms? Since we want to maintain a claim of plausibility and reasonableness we restrict ourselves to algorithmically easy to construct nets and we rule out infinite precision in parameters and in any analog parts of the computation. Our approach is to consider the recent advances in randomized algorithms and see if such randomized computations can be described by neural nets. We start with a pair of neurons and show that by connecting them with reciprocal inhibition and some tonic input, then the steady-state will be one neuron ON and one neuron OFF, but which neuron will be ON and which neuron will be OFF will be chosen at random (perhaps, it would be better to say that microscopic noise in the analog computation will be turned into a megascale random bit). We then show that we can build a small network that uses this random bit process to generate repeatedly random bits. This random bit generator can then be connected with a neural net representing the deterministic part of randomized algorithm. We, therefore, demonstrate that these neural nets can carry out probabilistic computation and thus be less limited than classical neural nets.     

Differentiation genes: are they primary targets for human carcinogenesis?

In spite of extensive research in molecular carcinogenesis, genes that can be considered primary targets in human carcinogenesis remain to be identified. Mutated oncogenes or cellular growth regulatory genes, when incorporated into normal human epithelial cells, failed to immortalize or transform these cells. Therefore, they may be secondary events in human carcinogenesis. Based on some experimental studies we have proposed that downregulation of a differentiation gene may be the primary event in human carcinogenesis. Such a gene could be referred to as a tumor-initiating gene. Downregulation of a differentiation gene can be accomplished by a mutation in the differentiation gene, by activation of differentiation suppressor genes, and by inactivation of tumor suppressor genes. Downregulation of a differentiation gene can lead to immortalization of normal cells. Mutations in cellular proto-oncogenes, growth regulatory genes, and tumor suppressor genes in immortalized cells can lead to transformation. Such genes could be called tumor-promoting genes. This hypothesis can be documented by experiments published on differentiation of neuroblastoma (NB) cells in culture. The fact that terminal differentiation can be induced in NB cells by adenosine 3',5'-cyclic monophosphate (cAMP) suggests that the differentiation gene in these cells is not mutated, and thus can be activated by an appropriate agent. The fact that cAMP-resistant cells exist in NB cell populations suggests that a differentiation gene is mutated in these cancer cells, or that differentiation regulatory genes have become unresponsive to cAMP. In addition to cAMP, several other differentiating agents have been identified. Our proposed hypothesis of carcinogenesis can also be applied to other human tumors such as melanoma, pheochromocytoma, medulloblastoma, glioma, sarcoma, and colon cancer.     

Digging and marble burying in mice: simple methods for in vivo identification of biological impacts

Mice exhibit various species-typical behaviors such as digging and burrowing. They dig in the ground to find food, to hoard food, to create a refuge from predators or cold and to make a safe nursery area for the young. In the laboratory, mice dig vigorously in deep bedding such as wood chips. This behavior is sensitive to strain differences and drugs. For example, the effects of anxiolytics and 5-HT-active compounds, including those used clinically for obsessive-compulsive disorder (OCD), can be detected. Digging can be quantified by manual timing. Alternatively, the bedding can be covered with glass marbles and the number buried can be counted after a set time. These behaviors can be assessed using very little specialized equipment, and results can be obtained from ten animals in about an hour. Species-typical behaviors may be sensitive to a wide variety of treatments, and their simplicity and ability to yield robust quantitative data might be particularly useful in assessing genetically modified mice, even in laboratories not primarily oriented to behavioral work.     

What is comparable in comparative cognition?

To understand how complex, or 'advanced' various forms of cognition are, and to compare them between species for evolutionary studies, we need to understand the diversity of neural-computational mechanisms that may be involved, and to identify the genetic changes that are necessary to mediate changes in cognitive functions. The same overt cognitive capacity might be mediated by entirely different neural circuitries in different species, with a many-to-one mapping between behavioural routines, computations and their neural implementations. Comparative behavioural research needs to be complemented with a bottom-up approach in which neurobiological and molecular-genetic analyses allow pinpointing of underlying neural and genetic bases that constrain cognitive variation. Often, only very minor differences in circuitry might be needed to generate major shifts in cognitive functions and the possibility that cognitive traits arise by convergence or parallel evolution needs to be taken seriously. Hereditary variation in cognitive traits between individuals of a species might be extensive, and selection experiments on cognitive traits might be a useful avenue to explore how rapidly changes in cognitive abilities occur in the face of pertinent selection pressures.     

Stem cell colloquy: conclusion

The stem cell data presented and discussed during the symposium raise the hope that important medical progress can be made in several fields: neuro-degenerative diseases, those linked to cellular deficit, some aspects of aging linked to cellular degeneration, and the treatment of cancers that may harm normal tissues at risk of being infiltrated by malignant cells. Three main types of stem cells are available. (i) Those present in normal adult tissue: contrary to what was believed, some data suggest that certain adult stem cells have a great plasticity (they can differentiate into cells different from those in tissues from which they were taken) and can proliferate in vitro without losing their properties. Nevertheless, their use faces several obstacles: in ill or elderly subjects, then these cells can be limited in number or not multiply well in vitro. In this case, auto-grafting of the cells cannot be used. They must be sought in another subject, and allo-grafting causes difficult and sometimes insoluble problems of immunological tolerance. (ii) Embryonic stem cells from surplus human embryos, obtained by in vitro fertilisation, which the parents decide not to use: these cells have a great potential for proliferation and differentiation, but can also encounter problems of immunological intolerance. (iii) Cells obtained from cell nuclear transfer in oocytes: these cells are well tolerated, since they are genetically and immunologically identical to those of the host. All types of stem cells can be obtained with them. However, they do present problems. For obtaining them, female oocytes are needed, which could lead to their commercialization. Moreover, the first steps for obtaining these cells are identical to those used in reproductive cloning. It therefore appears that each type of cell raises difficult scientific and practical problems. More research is needed to overcome these obstacles and to determine which type of stem cell constitutes the best solution for each type of disease and each patient. There are three main ethical problems: (a) to avoid the commercialization of stem cells and oocytes (this can be managed through strict regulations and the supervision of authorized laboratories); (b) to avoid that human embryos be considered as a mere means to an end (they should only be used after obtaining the informed consent of the parents; the conditions of their use must be well defined and research programs must be authorized); (c) to avoid that research on stem cell therapy using cell nuclear replacement opens the way to reproductive cloning (not only should reproductive cloning be firmly forbidden but authorization for cell nuclear transfer should be limited to a small number of laboratories). Overall, it appears that solutions can be found for administrative and ethical problems. Harmonisation of international regulations would be desirable in this respect, in allowing at the same time each country to be responsible for its regulations. A last ethical rule should be implemented, not to give patients and their families false hopes. The scientific and medical problems are many, and the solutions will be long and difficult to find. Regenerative medicine opens important avenues for research, but medical progress will be slow.     

Prediction of two- and three-amino-acid sequences of Citrobacter Freundii beta-lactamase from its amino acid composition

The repeated amino-acid sequences in Citrobacter Freundii beta-lactamase may be indispensable for its function, because such repetitions cannot be simply attributed to a chance. In order to fully explore the functional units in Citrobacter Freundii beta-lactamase, it may need to analyse all the amino acid pairs, triplets, etc. along Citrobacter Freundii beta-lactamase from one terminal to the other terminal, to count their frequencies and calculate their probabilities. The amino-acid sequence of Citrobacter Freundii beta-lactamase was counted according to two-, three- and four-amino-acid sequences. The counted frequency and probability were compared with the predicted frequency and probability. The amino acid sequences, which appear in Citrobacter Freundii beta-lactamase and can be predicted from its amino acid composition according to a purely random mechanism, should not be deliberately evolved and conserved. By contrast, the amino acid sequences, which appear in Citrobacter Freundii beta-lactamase but cannot be predicted from its amino acid composition according to a purely random mechanism, should be deliberately evolved and conversed. Accordingly 99 (26.053%) and 33 (8.684%) of 380 two-amino-acid sequences can be predicted by the frequency and probability according to a purely random mechanism. Some kinds of amino acid sequences, which absent in Citrobacter Freundii beta-lactamase and can be predicted from its amino acid composition according to a purely random mechanism, should not be deliberately excluded from Citrobacter Freundii beta-lactamase. By contrast, some kinds of amino acid sequences, which absent in Citrobacter Freundii beta-lactamase and cannot be predicted from its amino acid composition according to a purely random mechanism, should be deliberately excluded from Citrobacter Freundii beta-lactamase. Accordingly 89 (48.370%) and 41 (22.283%) of 184 kinds of absent two-amino-acid sequences can be predicted by the frequency and probability according to a purely random mechanism, and 7236 (99.848%) of 7247 kinds of absent three-amino-acid sequences can be predicted by the frequency according to a purely random mechanism. The amino acids, whose probabilities in following certain preceding amino acids can be predicted from Citrobacter Freundii beta-lactamase amino acid composition according to a purely random mechanism, should not be deliberately evolved and conversed, accordingly 2 (0.526%) of 380 counted first order Markov transition probabilities for the second amino acid in two-amino-acid sequences match the predicted conditional probabilities.     

Marital therapy for the elderly.

Little attention has been paid to marital therapy for the elderly in spite of its relevance to morale and emotional problems. Physical illness is of particular significance in altering the dynamics of the marital relationship. Retirement and financial problems, as well as changes in sexual activity and gender roles, are also important. However, radical changes in patterns of behaviour cannot be expected. Therapeutic techniques must be altered for this age group, and the therapist must be active, giving and concretely helpful. As with therapy for younger couples, children may need to be involved in the therapy sessions. Family physicians should be a main source of help for marital problems among the elderly. However, because problems related to countertransference must be faced, working with the elderly will not be for everyone.     

Alternative hypotheses for the effects of drugs in small-scale clinical studies

New drugs that will be investigated in the future are expected to deal with chronic diseases, where the number of patients available for controlled clinical trials will be small and where the long-term sequelae that it is hoped will be ameliorated take a long time to occur. Thus, it would be useful to construct powerful tests of hypotheses that can be used to compare subtle intermediate measures of change in condition. This paper examines the probabilistic characteristics of these measures and the changes in them that might be expected from drug therapy.     

Evolution and valuing

Human evolution can shed light on ethics through an account of valuing. This basic human activity is to be explained as a judgement on our desires in the light of a self appraisal with respect to desires of higher order. These concern what we desire to be and how we desire to lead a life. It is argued that the conditions of valuing may be found at least in primitive form in the use of language, which surely has an evolutionary explanation. But values may be trivial or false; to be ethically correct they must be authentic and objective. Because belief and desire are plastic to cultural influence, we cannot expect an evolutionary account of this last appraisal.     

Additional evidence for a proform to tropoelastin from chick aorta.

Evidence is presented for the presence of precursor to tropoelastin in chick arterial extracts. The precursor is approx. 100 000 daltons in size. It is suggested to be a precursor to tropoelastin (72 000 daltons). This protein may be observed in culture in vitro if appropriate precautions are taken to inhibit proteolysis. Once synthesized, it appears to be converted into tropoelastin within 10--20 min. The protein may also be detected in vivo. When 1-day-old cockerels were fed on a copper-deficient diet (less than 1 p.p.m. to inhibit cross-linking) containing epsilon-aminohexanoic acid (0.2%) to retard proteolysis and then injected wiht [3H]valine, extraction of arterial proteins 12h after injection resulted in detection of two major peaks of [3H]valine-labelled protein with pI values of pH 7.0 and 5.0 respectively. The protein that focused at pH 7.0 was estimated to be about 100 000 daltons in size and could be shown to be converted into a more basic protein with the properties of tropoelastin. It is speculated that the protein with pI 5.0 may be yet another extension peptide. The data appear to be in keeping with similar observations by ourselves and others that a proform of tropoelastin exists, and, in at least one step before conversion into tropoelastin, exists as a 100 000-dalton protein subunit.     

POSTURAL VERTIGO AND POSITIONAL NYSTAGMUS

Oscillation of the eyes of a patient when the head is placed in a certain position is objective evidence to support a complaint of postural vertigo—dizziness when the head is tilted forward or upward or turned to one side or the other. Since positional nystagmus may be difficult to evoke and may be elicited at one time and not at another, it is important to make repeated tests, lest a causative lesion be overlooked.Vertigo in such cases may be caused by pathologic change in the eighth peripheral nerve or in the central vestibular pathways. Sometimes no organic disease is observable even though positional nystagmus validates a complaint of vertigo. In such instances the patient should be assured that he does not have a progressive disease and be advised against activity in which dizziness would be hazardous.