Interactive Multi-Domain System Analysis and Design

Abstract This paper presents a MATLAB tool for interactive transfer function analysis which can be used to enhance students and engineers understanding of system characteristics and behaviour. It allows a user to develop an intuitive feeling for the relationship between time and frequency domains, and locations of roots of a transfer function

Modeling and identification of a class of servomechanism systems with stick-slip friction

This paper describes a technique for modeling and identifying a class of nonlinear servomechanism systems with stick-slip friction. The physics of the stick-slip friction is considered in modeling the process. Identification of the system parameters is formulated as a nonlinear optimization problem. A modified simplex algorithm is pro- I Introduction When operating with small amplitude and low frequency signal input, the presence of stick-slip friction in a servomechanism cannot be ignored. To accurately predict or simulate the performance of the system, the effects of friction on the motor behavior should be taken into consideration by appropriate modeling of the friction. This paper describes a modeling and identification technique for a class of servomechanism systems with stick-slip friction. In the paper [1], Karnopp presented a novel model for describing the effect of stick-slip friction in mechanical dynamic systems. The model proposed by Karnopp takes the physics of the stick-slip friction process into account by considering the rate of change of momentum in the mechanical system. The main parameters in the model include the inertia of the system, the slip coefficient, the threshold for the momentum rate and the saturation stick force. The stick-slip friction model of Karnopp is adapted to a class of servomechanism in this paper. For the present discussion, the dc servomotor is considered. The proposed adaptation can be extended to other classes of servomechanisms. This paper next addresses an identification technique and the choice of input signals for estimating the parameters associated with the nonlinear stick-slip model. The identification problem is posed as an optimization problem to be solved using nonlinear programming methods II Modeling A typical armature-controlled dc motor is shown in 324/Vol. 110, SEPTEMBER 1988 The schematic block diagram for the system is given in The friction torque T f consists of two components, r s i ip and r stick . In the slip region where \6 m \>Dj, the switching Rm Lrr Transactions of the AS M

The SMC-5/6 Complex and the HIM-6 (BLM) Helicase Synergistically Promote Meiotic Recombination Intermediate Processing and Chromosome Maturation during<i> Caenorhabditis elegans</i> Meiosis

Meiotic recombination is essential for the repair of programmed double strand breaks (DSBs) to generate crossovers (COs) during meiosis. The efficient processing of meiotic recombination intermediates not only needs various resolvases but also requires proper meiotic chromosome structure. The Smc5/6 complex belongs to the structural maintenance of chromosome (SMC) family and is closely related to cohesin and condensin. Although the Smc5/6 complex has been implicated in the processing of recombination intermediates during meiosis, it is not known how Smc5/6 controls meiotic DSB repair. Here, using Caenorhabditis elegans we show that the SMC-5/6 complex acts synergistically with HIM-6, an ortholog of the human Bloom syndrome helicase (BLM) during meiotic recombination. The concerted action of the SMC-5/6 complex and HIM-6 is important for processing recombination intermediates, CO regulation and bivalent maturation. Careful examination of meiotic chromosomal morphology reveals an accumulation of inter-chromosomal bridges in smc-5; him-6 double mutants, leading to compromised chromosome segregation during meiotic cell divisions. Interestingly, we found that the lethality of smc-5; him-6 can be rescued by loss of the conserved BRCA1 ortholog BRC-1. Furthermore, the combined deletion of smc-5 and him-6 leads to an irregular distribution of condensin and to chromosome decondensation defects reminiscent of condensin depletion. Lethality conferred by condensin depletion can also be rescued by BRC-1 depletion. Our results suggest that SMC-5/6 and HIM-6 can synergistically regulate recombination intermediate metabolism and suppress ectopic recombination by controlling chromosome architecture during meiosis

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment

Variation in the human genome is a most important cause of variable response to drugs and other xenobiotics. Susceptibility to almost all diseases is determined to some extent by genetic variation. Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general. Nowadays we can assess more than 1,000,000 polymorphisms or the expression of more than 25,000 genes in each participant of a clinical study – at affordable costs. This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice. More obviously, pharmacogenetics has changed the practices and requirements in preclinical and clinical drug research; large clinical trials without a pharmacogenomic add-on appear to have become the minority. This review is about how the discipline of pharmacogenetics has evolved from the analysis of single proteins to current approaches involving the broad analyses of the entire genome and of all mRNA species or all metabolites and other approaches aimed at trying to understand the entire biological system. Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance