Research on optimization-based design

Research on optimization-based design is discussed. Illustrative examples are given for cases involving continuous optimization with discrete variables and optimization with tolerances. Approximation of computationally expensive and noisy functions, electromechanical actuator/control system design using decomposition and application of knowledge-based systems and optimization for the design of a valve anti-cavitation device are among the topics covered

Execution of Multidisciplinary Design Optimization Approaches on Common Test Problems

A class of synthetic problems for testing multidisciplinary design optimization (MDO) approaches is presented. These test problems are easy to reproduce because all functions are given as closed-form mathematical expressions. They are constructed in such a way that the optimal value of all variables and the objective is unity. The test problems involve three disciplines and allow the user to specify the number of design variables, state variables, coupling functions, design constraints, controlling design constraints, and the strength of coupling. Several MDO approaches were executed on two sample synthetic test problems. These approaches included single-level optimization approaches, collaborative optimization approaches, and concurrent subspace optimization approaches. Execution results are presented, and the robustness and efficiency of these approaches an evaluated for these sample problems

Optimization of coupled systems: A critical overview of approaches

A unified overview is given of problem formulation approaches for the optimization of multidisciplinary coupled systems. The overview includes six fundamental approaches upon which a large number of variations may be made. Consistent approach names and a compact approach notation are given. The approaches are formulated to apply to general nonhierarchic systems. The approaches are compared both from a computational viewpoint and a managerial viewpoint. Opportunities for parallelism of both computation and manpower resources are discussed. Recommendations regarding the need for future research are advanced

An algorithm for solving the system-level problem in multilevel optimization

A multilevel optimization approach which is applicable to nonhierarchic coupled systems is presented. The approach includes a general treatment of design (or behavior) constraints and coupling constraints at the discipline level through the use of norms. Three different types of norms are examined: the max norm, the Kreisselmeier-Steinhauser (KS) norm, and the 1(sub p) norm. The max norm is recommended. The approach is demonstrated on a class of hub frame structures which simulate multidisciplinary systems. The max norm is shown to produce system-level constraint functions which are non-smooth. A cutting-plane algorithm is presented which adequately deals with the resulting corners in the constraint functions. The algorithm is tested on hub frames with increasing number of members (which simulate disciplines), and the results are summarized

Embryonic development of selectively vulnerable neurons in Parkinson's disease

A specific set of brainstem nuclei are susceptible to degeneration in Parkinson’s disease. We hypothesise that neuronal vulnerability reflects shared phenotypic characteristics that confer selective vulnerability to degeneration. Neuronal phenotypic specification is mainly the cumulative result of a transcriptional regulatory program that is active during the development. By manual curation of the developmental biology literature, we comprehensively reconstructed an anatomically resolved cellular developmental lineage for the adult neurons in five brainstem regions that are selectively vulnerable to degeneration in prodromal or early Parkinson’s disease. We synthesised the literature on transcription factors that are required to be active, or required to be inactive, in the development of each of these five brainstem regions, and at least two differentially vulnerable nuclei within each region. Certain transcription factors, e.g., Ascl1 and Lmx1b, seem to be required for specification of many brainstem regions that are susceptible to degeneration in early Parkinson’s disease. Some transcription factors can even distinguish between differentially vulnerable nuclei within the same brain region, e.g., Pitx3 is required for specification of the substantia nigra pars compacta, but not the ventral tegmental area. We do not suggest that Parkinson’s disease is a developmental disorder. In contrast, we consider identification of shared developmental trajectories as part of a broader effort to identify the molecular mechanisms that underlie the phenotypic features that are shared by selectively vulnerable neurons. Systematic in vivo assessment of fate determining transcription factors should be completed for all neuronal populations vulnerable to degeneration in early Parkinson’s disease

Fluorochrome Bone Labeling in Sheep

As an efficacy model. thirty-four female Merino sheep underwent transpedicular lumbar interbody fusion with three different materials for augmentation of the spine. Fluorochrome analysis was used to evaluate differences in bone deposition and fusion processes between the three study groups. During the post-operative follow-up period ofeight weeks, the fluorescent dyes xylenol orange. calcein green, and doxyeycline yellow were given at two, four. and six weeks, respectively. All dyes were administered intravenously after sedation with xylazine. The objective of this paper is to provide a methodical description of preparation quality control, administration, efficacy, and observed adverse events from the use of these bone labels in sheep.Both xylenol orange and calcein green dyes provided satisfying results but doxycyeline yellow led to only weak fluorescence in the first ten animals. Consequently, higher dosing was introduced to obtain bright bands in the histological sections. Also, during administration of doxycyeline yellow, mild to severe adverse events occasionally occured: Eight of the first ten sheep suffered from respiratory distress, and in severe cases several stopped breathing, thus requiring immediate intervention. Minimizing the sedative dose and elongating the sedation/doxycycline administration interval were effective changes to the original procedure. We conclude that these adverse events may have been caused by too high a close of sedative, as well as a drug interaction between xylazine and doxycycline yellow

A family of octamer-specific proteins present during mouse embryogenesis: Evidence for germline-specific expression of an Oct factor.

We have analysed various adult organs and different developmental stages of mouse embryos for the presence of octamer-binding proteins. A variety of new octamer-binding proteins were identified in addition to the previously described Oct1 and Oct2. Oct1 is ubiquitously present in murine tissues, in agreement with cell culture data. Although Oct2 has been described as a B-cell-specific protein, similar complexes were also found with extracts from brain, kidney, embryo and sperm. In embryo and brain at least two other proteins, Oct3 and Oct7, are present. A new microextraction procedure allowed the detection of two maternally expressed octamer-binding proteins, Oct4 and Oct5. Both proteins are present in unfertilized oocytes and embryonic stem cells, the latter containing an additional protein, Oct6. Whereas Oct4 was not found in sperm or testis, it is expressed in male and female primordial germ cells. Therefore Oct4 expression is specific for the female germline at later stages of germ cell development. Our results indicate that a family of octamer-binding proteins is present during mouse development and is differentially expressed during early embryogenesis. Protease clipping experiments of Oct4 and Oct1 suggest that both proteins contain similar DNA-binding domains

Octamer binding proteins confer transcriptional activity in early mouse embryogenesis.

Oct4 and Oct5 are two mouse maternally expressed proteins binding to the octamer motif. Both are found in unfertilized oocytes and embryonic stem cells, whereas Oct4 is also found in primordial germ cells. In this study, the activity of the octamer motif was analysed in two embryonic stem cell lines containing Oct4 and Oct5, the teratocarcinoma-derived cell line F9 and the blastocyst-derived cell line D3. It is known that oligomerization of the octamer motif creates a powerful B-cell specific enhancer. As shown here, this oligomerized transcriptional element is also a very strong enhancer in F9 and D3 embryonic stem cells. After differentiation of the stem cells, both enhancer activity and the amount of the octamer binding proteins decrease. An intact octamer stimulates heterologous promoters in embryonic stem cells, whereas mutations in the octamer motif abolish transcriptional stimulation and binding of the octamer factors. The use of transgenic embryos demonstrates transcriptional activation in the inner cell mass but not in the trophoblast of blastocysts. The results indicate that Oct4 and Oct5 are active early in mouse development