Planning complex engineer-to-order products

The design and manufacture of complex Engineer-to-Order products is characterised by uncertain operation durations, finite capacity resources and multilevel product structures. Two scheduling methods are presented to minimise expected costs for multiple products across multiple finite capacity resources. The first sub-optimises the operations sequence, using mean operation durations, then refines the schedule by perturbation. The second method generates a schedule of start times directly by random search with an embedded simulation of candidate schedules for evaluation. The methods are compared for industrial examples

Neuroimaging in anxiety disorders

Neuroimaging studies have gained increasing importance in validating neurobiological network hypotheses for anxiety disorders. Functional imaging procedures and radioligand binding studies in healthy subjects and in patients with anxiety disorders provide growing evidence of the existence of a complex anxiety network, including limbic, brainstem, temporal, and prefrontal cortical regions. Obviously, “normal anxiety” does not equal “pathological anxiety” although many phenomena are evident in healthy subjects, however to a lower extent. Differential effects of distinct brain regions and lateralization phenomena in different anxiety disorders are mentioned. An overview of neuroimaging investigations in anxiety disorders is given after a brief summary of results from healthy volunteers. Concluding implications for future research are made by the authors

Phage φ29 DNA Replication Organizer Membrane Protein p16.7 Contains a Coiled Coil and a Dimeric, Homeodomain-related, Functional Domain

The Bacillus subtilis phage φ29-encoded membrane protein p16.7 is one of the few proteins known to be involved in prokaryotic membrane-associated DNA replication. Protein p16.7 contains an N-terminal transmembrane domain responsible for membrane localization. A soluble variant lacking the N-terminal membrane anchor, p16.7A, forms dimers in solution, binds to DNA, and has affinity for the φ29 terminal protein. Here we show that the soluble N-terminal half of p16.7A can form a dimeric coiled coil. However, a second domain, located in the C-terminal half of the protein, has been characterized as being the main domain responsible for p16.7 dimerization. This 70-residue C-terminal domain, named p16.7C, also constitutes the functional part of the protein as it binds to DNA and terminal protein. Sequence alignments, secondary structure predictions, and spectroscopic analyses suggest that p16.7C is evolutionarily related to DNA binding homeodomains, present in many eukaryotic transcriptional regulator proteins. Based on the results, a structural model of p16.7 is presented.This work was supported in part by Research Grant 2RO1 GM27242-24 from the National Institutes of Health (to M. S.) and by Grants BIO2003-04445 (to M. G. M.) and BMC2002-03818 (to M. S.) from the Spanish Ministry of Science and Technology. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.Peer reviewe

Herpesvirus saimiri.

Herpesvirus saimiri (saimiriine herpesvirus 2) is the classical prototype of the gamma(2)-herpesviruses or rhadinoviruses, which also contains a human member, the Kaposi's sarcoma-associated herpesvirus. The T-lymphotropic Herpesvirus saimiri establishes specific replicative and persistent conditions in different primate host species. Virtually all squirrel monkeys (Saimiri sciureus) are persistently infected with this virus. In its natural host, the virus does not cause disease, whereas it induces fatal acute T-cell lymphoma in other monkey species after experimental infection. The virus can be isolated by cocultivation of permissive epithelial cells with peripheral blood cells from naturally infected squirrel monkeys and from susceptible New World monkeys during the virus-induced disease. Tumour-derived and in vitro-transformed T-cell lines from New World monkeys release virus particles. Herpesvirus ateles is a closely related virus of spider monkeys (Ateles spp.) and has similar pathogenic properties to Herpesvirus saimiri in other New World primate species. Similar to other rhadinoviruses, the genome of Herpesvirus saimiri harbours a series of virus genes with pronounced homology to cellular counterparts including a D-type cyclin, a G-protein-coupled receptor, an interleukin-17, a superantigen homologue, and several inhibitors of the complement cascade and of different apoptosis pathways. Preserved function has been demonstrated for most of the homologues of cellular proteins. These viral functions are mostly dispensable for the transforming and pathogenic capability of the virus. However, they are considered relevant for the apathogenic persistence of Herpesvirus saimiri in its natural host. A terminal region of the non-repetitive coding part of the virus genome is essential for pathogenicity and T-cell transformation. Based on the pathogenic phenotypes and the different alleles of this variable region, the virus strains have been assigned to three subgroups, termed A, B and C. In the highly oncogenic subgroup C strains, the two virus genes stpC and tip are transcribed from one bicistronic mRNA and are essential for transformation and leukaemia induction. stpC fulfils the typical criteria of an oncogene; its product interacts with Ras and tumour necrosis factor-associated factors and induces mitogen-activated protein kinase and nuclear factor kappa B activation. Tip interacts with the RNA transport factor Tap, with signal transduction and activation of transcription factors, and with the T-cellular tyrosine kinase Lck, which is activated by this interaction and phosphorylates Tip as a substrate. It is of particular interest that certain subgroup C virus strains such as C488 are capable of transforming human T lymphocytes to stable growth in culture. The transformed human T cells harbour multiple copies of the viral genome in the form of stable, non-integrated episomes. The cells express only a few virus genes and do not produce virus particles. The transformed cells maintain the antigen specificity and many other essential functions of their parental T-cell clones. Based on the preserved functional phenotype of the transformed T cells, Herpesvirus saimiri provides useful tools for T-cell immunology, for gene transfer and possibly also for experimental adoptive immunotherapy